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A rare primary immunodeficiency with autosomal or X-linked recessive inheritance, characterized by atrophy of the thymus in the absence of other congenital abnormalities, with profound T-cell deficiency, while serum immunoglobulin levels are normal or increased. Patients present with chronic or recurrent infections in infancy including candidiasis, skin, pulmonary and urinary tract infections, chronic diarrhea, and failure to thrive. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Thymic aplasia	c0152094	3,900	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83471	2021-01-23T17:57:25	{"gard": ["7201"], "mesh": ["C536288"], "omim": ["242700"], "umls": ["C0152094", "C0685894"], "icd-10": ["D81.4"], "synonyms": ["Nezelof syndrome"]}
A rare, genetic, lypmhoproliferative syndrome characterized by early onset recurrent infections, lymphadenopathy with hepatosplenomegaly and variabe autoimmune disorders, including hemolytic anemia, thrombocytopenia, neutropenia, enteropathy, type I diabetes, scleroderma, arthritis, atopic dermatitis, and inflammatory lung disease. Patients commonly have failure to thrive. Variable immunologic findings include decreased regulatory T-cells, hypogammaglobulinemia, and reduction in memory 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	STAT3-related early-onset multisystem autoimmune disease	c4014795	3,901	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=438159	2021-01-23T16:56:42	{"omim": ["615952"], "icd-10": ["M35.8"]}
A rare otorhinolaryngological malformation characterized by a hypoplastic or absent cochlear nerve, resulting in variable hearing loss or total deafness, depending on the quantity of nerve fibers present. The condition can be unilateral or bilateral, occur as an isolated malformation or in the context of a complex syndrome, and may be associated with a hypoplastic internal auditory or cochlear nerve canal. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Cochlear nerve deficiency	None	3,902	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=502318	2021-01-23T17:23:33	{}
Urachal cancer Micrograph of urachal carcinoma (right of image) and non-malignant urothelium (left of image). H&E stain. SpecialtyOncology Urachal cancer is a very rare type of cancer arising from the urachus or its remnants.[1] The disease might arise from metaplasic glandular epithelium or embryonic epithelial remnants originating from the cloaca region.[2] It occurs in roughly about one person per 1 million people per year varying on the geographical region.[3] Men are affected slightly more often than women mostly in the 5th decade of life but the disease can occur in also in other age groups.[4][5] It can involve the urinary bladder, but is not bladder cancer in the usual sense. Urachal cancer can occur at any site along the urachal tract. Urachal cancer was mentioned by Hue and Jacquin in 1863 followed by an elaborate work by T. Cullen in 1916 about diseases of the umbilicus, while C. Begg further characterized urachal cancer in the 1930s.[2][6] Detailed diagnostic and staging schemes were proposed by Sheldon et al in 1984, which remain widely used today.[1] ## Contents * 1 Classification * 2 Symptoms and Signs * 3 Causes * 4 Mechanism * 5 Diagnosis * 5.1 Histopathological Diagnosis * 5.2 Imaging * 6 Prevention * 7 Treatment * 7.1 Serum Markers for Monitoring * 8 Outcomes * 9 Epidemiology * 10 History * 11 References * 12 External links ## Classification[edit] Urachal cancer usually is an adenocarcinoma (about 90%) mostly with mucinous/colloidal histology. Other rare types include urothelial carcinoma, squamous cell carcinoma, neuroendocrine carcinoma and sarcoma.[2][4][7] ## Symptoms and Signs[edit] Urachal cancer can exist for some years without any symptoms. The most frequent initial symptom is haematuria which occurs when the urachal tumour has penetrated the bladder wall, but mucinuria (mucin in the urine), local pain or swelling, recurrent local or urinary tract infections and umbilical discharge can (but is not always) be seen.[4][5] ## Causes[edit] This section is empty. You can help by adding to it. (July 2020) ## Mechanism[edit] This section is empty. You can help by adding to it. (July 2020) ## Diagnosis[edit] According to the American Urological Association, the diagnostic criteria are the following:[8] 1. The location of the tumor is mostly at the bladder dome. 2. No findings of cystitis glandularis on the bladder surface. These findings can be precursor lesions of a primary bladder adenocarcinoma. 3. No history of a different primary adenocarcinoma with the same morphology. Tissue for histological analysis is usually obtained via a transurethral resection of bladder tumor (TURBT). ### Histopathological Diagnosis[edit] A case of urachal adenocarcinoma demonstrating immunohistochemical CDX2-positivity with typical nuclear staining. 200x magnification. According to the American Urological Association, the histologic findings are the following:[8] 1. Mucinous carcinoma (tumor cells within mucin microcollections) 2. Enteric morphology (i.e. colorectal adenocarcinoma), 3. Other morphologies: signet ring cell, adenocarcinoma, mixed, or unclassifiable. 4. Immunohistochemical staining (CDX2+, CK7+, β-catenin-) ### Imaging[edit] CT and MRI scans are useful to evaluate local invasion and metastasis to lymph nodes and other parts of the body. Besides, in 32 to 46% of the cases, they show calcifications which is very suggestive of the disease.[9] ## Prevention[edit] This section is empty. You can help by adding to it. (July 2020) ## Treatment[edit] Surgical management is en bloc resection of bladder, urachal remnant, and umbilicus.[8] In progressed stages, radiotherapy seems not to lead to sufficient response rates. However, chemotherapy regimes containing 5-FU (and Cisplatin) have been described to be useful in these cases.[4][10] In recent years, targeted therapies have been demonstrated to be useful in reports of single cases. These agents included Sunitinib,[11] Gefitinib,[12] Bevacizumab[13] and Cetuximab.[14] ### Serum Markers for Monitoring[edit] Measurement of serum concentrations of CEA, CA19-9 and CA125 can be helpful in monitoring urachal cancer[2][15] ## Outcomes[edit] The 5-year survival is estimated between 25 and 61%.[8] Worse prognostic factors include the presence of residual tumor at the margin of the resection specimen (R+), invasion of the peritoneum and metastatic disease.[4] ## Epidemiology[edit] This section is empty. You can help by adding to it. (July 2020) ## History[edit] This section is empty. You can help by adding to it. (July 2020) ## References[edit] 1. ^ a b Sheldon, C. A.; Clayman, R. V.; Gonzalez, R.; Williams, R. D.; Fraley, E. E. (1984-01-01). "Malignant urachal lesions". The Journal of Urology. 131 (1): 1–8. doi:10.1016/s0022-5347(17)50167-6. ISSN 0022-5347. PMID 6361280. 2. ^ a b c d Paner, Gladell P.; Lopez-Beltran, Antonio; Sirohi, Deepika; Amin, Mahul B. (2016-03-01). "Updates in the Pathologic Diagnosis and Classification of Epithelial Neoplasms of Urachal Origin". Advances in Anatomic Pathology. 23 (2): 71–83. doi:10.1097/PAP.0000000000000110. ISSN 1533-4031. PMID 26849813. 3. ^ Bruins, H. Max; Visser, Otto; Ploeg, Martine; Hulsbergen-van de Kaa, Christina A.; Kiemeney, Lambertus A. L. M.; Witjes, J. Alfred (2012-10-01). "The clinical epidemiology of urachal carcinoma: results of a large, population based study". The Journal of Urology. 188 (4): 1102–1107. doi:10.1016/j.juro.2012.06.020. ISSN 1527-3792. PMID 22901574. 4. ^ a b c d e Szarvas, Tibor; Módos, Orsolya; Niedworok, Christian; Reis, Henning; Szendröi, Attila; Szász, Marcell A.; Nyirády, Péter (2016-06-03). "Clinical, prognostic, and therapeutic aspects of urachal carcinoma-A comprehensive review with meta-analysis of 1,010 cases". Urologic Oncology. 34 (9): 388–398. doi:10.1016/j.urolonc.2016.04.012. ISSN 1873-2496. PMID 27267737. 5. ^ a b Behrendt, Mark A.; DE Jong, Jeroen; VAN Rhijn, Bas W. (2016-04-01). "Urachal cancer: contemporary review of the pathological, surgical, and prognostic aspects of this rare disease". Minerva Urologica e Nefrologica. 68 (2): 172–184. ISSN 0393-2249. PMID 26583595. 6. ^ Begg, RC (1931). "The colloid adenocarcinomata of the bladder vault arising from the epithelium of the urachal canal: with a critical survey of the tumours of the urachus". Br J Surg. 18 (71): 422–466. doi:10.1002/bjs.1800187108. 7. ^ Wright, Jonathan L.; Porter, Michael P.; Li, Christopher I.; Lange, Paul H.; Lin, Daniel W. (2006-08-15). "Differences in survival among patients with urachal and nonurachal adenocarcinomas of the bladder". Cancer. 107 (4): 721–728. doi:10.1002/cncr.22059. ISSN 0008-543X. PMID 16826584. 8. ^ a b c d "Urachal Adenocarcinoma". AUAnet.org. 9. ^ Claps, Mélanie; Stellato, Marco; Zattarin, Emma; Mennitto, Alessia; Sepe, Pierangela; Guadalupi, Valentina; Mennitto, Roberta; de Braud, Filippo G.M.; Verzoni, Elena; Procopio, Giuseppe (January 2020). "Current Understanding of Urachal Adenocarcinoma and Management Strategy". Current Oncology Reports. 22 (1): 9. doi:10.1007/s11912-020-0878-z. ISSN 1523-3790. 10. ^ Siefker-Radtke, Arlene (2012-10-01). "Urachal adenocarcinoma: a clinician's guide for treatment". Seminars in Oncology. 39 (5): 619–624. doi:10.1053/j.seminoncol.2012.08.011. ISSN 1532-8708. PMID 23040259. 11. ^ Testa, Isabella; Verzoni, Elena; Grassi, Paolo; Colecchia, Maurizio; Panzone, Filomena; Procopio, Giuseppe (2014-10-27). "Response to targeted therapy in urachal adenocarcinoma". Rare Tumors. 6 (4): 5529. doi:10.4081/rt.2014.5529. ISSN 2036-3605. PMC 4274441. PMID 25568747. 12. ^ Goss, G.; Hirte, H.; Miller, W. H.; Lorimer, I. a. J.; Stewart, D.; Batist, G.; Parolin, D. a. E.; Hanna, P.; Stafford, S. (2005-03-01). "A phase I study of oral ZD 1839 given daily in patients with solid tumors: IND.122, a study of the Investigational New Drug Program of the National Cancer Institute of Canada Clinical Trials Group". Investigational New Drugs. 23 (2): 147–155. doi:10.1007/s10637-005-5860-y. ISSN 0167-6997. PMID 15744591. 13. ^ Kanamaru, Tomohiro; Iguchi, Taro; Yukimatsu, Nao; Shimizu, Yasuomi; Kohyama, Yuki; Tachibana, Hirokazu; Kato, Minoru; Yamasaki, Takeshi; Tamada, Satoshi (2015-03-01). "A Case of Metastatic Urachal Carcinoma Treated With FOLFIRI (irinotecan and 5-Fluorouracil/leucovorin) Plus Bevacizumab". Urology Case Reports. 3 (2): 9–11. doi:10.1016/j.eucr.2014.11.004. ISSN 2214-4420. PMC 4714276. PMID 26793485. 14. ^ Collazo-Lorduy, Ana; Castillo-Martin, Mireia; Wang, Li; Patel, Vaibhav; Iyer, Gopa; Jordan, Emmet; Al-Ahmadie, Hikmat; Leonard, Issa; Oh, William K. (2016-05-10). "Urachal Carcinoma Shares Genomic Alterations with Colorectal Carcinoma and May Respond to Epidermal Growth Factor Inhibition". European Urology. 70 (5): 771–775. doi:10.1016/j.eururo.2016.04.037. ISSN 1873-7560. PMC 5489411. PMID 27178450. 15. ^ Siefker-Radtke, Arlene O.; Gee, Jason; Shen, Yu; Wen, Sijin; Daliani, Danai; Millikan, Randall E.; Pisters, Louis L. (2003-04-01). "Multimodality management of urachal carcinoma: the M. D. Anderson Cancer Center experience". The Journal of Urology. 169 (4): 1295–1298. doi:10.1097/01.ju.0000054646.49381.01. ISSN 0022-5347. PMID 12629346. ## External links[edit] Classification D * MeSH: C536475 External resources * eMedicine: radio/727 * Urachal cancer page from the National Institutes of Health * Urachal cancer page from the European Association of Urology - Patient Information * Urachal cancer page from urachal cancer researchers (UrachalCancer.org) * v * t * e Tumors of the urinary and genital systems Kidney Glandular and epithelial neoplasm * Renal cell carcinoma * Renal oncocytoma Mixed tumor * Wilms' tumor * Mesoblastic nephroma * Clear-cell sarcoma of the kidney * Angiomyolipoma * Cystic nephroma * Metanephric adenoma by location * Renal medullary carcinoma * Juxtaglomerular cell tumor * Renal medullary fibroma Ureter * Ureteral neoplasm Bladder * Transitional cell carcinoma * Squamous-cell carcinoma * Inverted papilloma Urethra * Transitional cell carcinoma * Squamous-cell carcinoma * Adenocarcinoma * Melanoma Other * Malignant fibrous histiocytoma [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Urachal cancer	c0153615	3,903	wikipedia	https://en.wikipedia.org/wiki/Urachal_cancer	2021-01-18T18:57:48	{"gard": ["7836"], "mesh": ["C536475"], "umls": ["C0153615"], "wikidata": ["Q7899541"]}
Lattice corneal dystrophy type I is an eye disorder that affects the clear, outer covering of the eye called the cornea. The cornea must remain clear for an individual to see properly; however, in lattice corneal dystrophy type I, protein clumps known as amyloid deposits cloud the cornea, which leads to vision impairment. The cornea is made up of several layers of tissue, and in lattice corneal dystrophy type I, the deposits form in the stromal layer. The amyloid deposits form as delicate, branching fibers that create a lattice pattern. Affected individuals often have recurrent corneal erosions, which are caused by separation of particular layers of the cornea from one another. Corneal erosions are very painful and can cause sensitivity to bright light (photophobia). Lattice corneal dystrophy type I is usually bilateral, which means it affects both eyes. The condition becomes apparent in childhood or adolescence and leads to vision problems by early adulthood. ## Frequency Lattice corneal dystrophy type I is one of the most common disorders in a group of conditions that are characterized by protein deposits in the cornea (corneal dystrophies); however, it is still a rare condition. The prevalence of lattice corneal dystrophy type I is unknown. ## Causes Lattice corneal dystrophy type I is caused by mutations in the TGFBI gene. This gene provides instructions for making a protein that is found in many tissues throughout the body, including the cornea. The TGFBI protein is part of the extracellular matrix, an intricate network that forms in the spaces between cells and provides structural support to tissues. The protein is thought to play a role in the attachment of cells to one another (cell adhesion) and cell movement (migration). The TGFBI gene mutations involved in lattice corneal dystrophy type I change single protein building blocks (amino acids) in the TGFBI protein. Mutated TGFBI proteins abnormally clump together and form amyloid deposits. However, it is unclear how the changes caused by the gene mutations induce the protein to form deposits. ### Learn more about the gene associated with Lattice corneal dystrophy type I * TGFBI ## Inheritance Pattern This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Lattice corneal dystrophy type I	c1690006	3,904	medlineplus	https://medlineplus.gov/genetics/condition/lattice-corneal-dystrophy-type-i/	2021-01-27T08:25:34	{"gard": ["9678"], "mesh": ["C537881"], "omim": ["122200"], "synonyms": []}
Pleomorphic lipoma SpecialtyOncology Pleomorphic lipomas, like spindle-cell lipomas, occur for the most part on the backs and necks of elderly men, and are characterized by floret giant cells with overlapping nuclei.[1]:625 ## See also[edit] * Lipoma * Skin lesion * List of cutaneous conditions ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. ## External links[edit] Classification D * ICD-O: 8854/0 * v * t * e Connective/soft tissue tumors and sarcomas Not otherwise specified * Soft-tissue sarcoma * Desmoplastic small-round-cell tumor Connective tissue neoplasm Fibromatous Fibroma/fibrosarcoma: * Dermatofibrosarcoma protuberans * Desmoplastic fibroma Fibroma/fibromatosis: * Aggressive infantile fibromatosis * Aponeurotic fibroma * Collagenous fibroma * Diffuse infantile fibromatosis * Familial myxovascular fibromas * Fibroma of tendon sheath * Fibromatosis colli * Infantile digital fibromatosis * Juvenile hyaline fibromatosis * Plantar fibromatosis * Pleomorphic fibroma * Oral submucous fibrosis Histiocytoma/histiocytic sarcoma: * Benign fibrous histiocytoma * Malignant fibrous histiocytoma * Atypical fibroxanthoma * Solitary fibrous tumor Myxomatous * Myxoma/myxosarcoma * Cutaneous myxoma * Superficial acral fibromyxoma * Angiomyxoma * Ossifying fibromyxoid tumour Fibroepithelial * Brenner tumour * Fibroadenoma * Phyllodes tumor Synovial-like * Synovial sarcoma * Clear-cell sarcoma Lipomatous * Lipoma/liposarcoma * Myelolipoma * Myxoid liposarcoma * PEComa * Angiomyolipoma * Chondroid lipoma * Intradermal spindle cell lipoma * Pleomorphic lipoma * Lipoblastomatosis * Spindle cell lipoma * Hibernoma Myomatous general: * Myoma/myosarcoma smooth muscle: * Leiomyoma/leiomyosarcoma skeletal muscle: * Rhabdomyoma/rhabdomyosarcoma: Embryonal rhabdomyosarcoma * Sarcoma botryoides * Alveolar rhabdomyosarcoma * Leiomyoma * Angioleiomyoma * Angiolipoleiomyoma * Genital leiomyoma * Leiomyosarcoma * Multiple cutaneous and uterine leiomyomatosis syndrome * Multiple cutaneous leiomyoma * Neural fibrolipoma * Solitary cutaneous leiomyoma * STUMP Complex mixed and stromal * Adenomyoma * Pleomorphic adenoma * Mixed Müllerian tumor * Mesoblastic nephroma * Wilms' tumor * Malignant rhabdoid tumour * Clear-cell sarcoma of the kidney * Hepatoblastoma * Pancreatoblastoma * Carcinosarcoma Mesothelial * Mesothelioma * Adenomatoid tumor This Dermal and subcutaneous growths article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Pleomorphic lipoma	c0205823	3,905	wikipedia	https://en.wikipedia.org/wiki/Pleomorphic_lipoma	2021-01-18T18:32:26	{"mesh": ["D008067"], "umls": ["C0205823"], "wikidata": ["Q7204592"]}
Cerebrovascular disorder Intracranial aneurysm Other namesCerebral aneurysm, brain aneurism, brain aneurysm, cerebral aneurism Aneurysm of the basilar artery and the vertebral arteries. SpecialtyInterventional neuroradiology, neurosurgery SymptomsNone, severe headache, visual problems, nausea and vomiting, confusion[1] Usual onset30–60 years old CausesHypertension, infection, head trauma[2] Risk factorsSmoking, old age, family history, cocaine use[1] Diagnostic methodAngiography, CT scan TreatmentEndovascular coiling, surgical clipping, cerebral bypass surgery An intracranial aneurysm, also known as a brain aneurysm, is a cerebrovascular disorder in which weakness in the wall of a cerebral artery or vein causes a localized dilation or ballooning of the blood vessel. Aneurysms in the posterior circulation (basilar artery, vertebral arteries and posterior communicating artery) have a higher risk of rupture. Basilar artery aneurysms represent only 3–5% of all intracranial aneurysms but are the most common aneurysms in the posterior circulation. ## Contents * 1 Classification * 1.1 Saccular aneurysms * 1.2 Fusiform aneurysms * 1.3 Microaneurysms * 2 Signs and symptoms * 2.1 Subarachnoid bleed * 2.2 Microaneurysms * 2.3 Vasospasm * 3 Risk factors * 3.1 Genetic associations * 4 Pathophysiology * 4.1 Saccular aneurysms * 5 Diagnosis * 6 Treatment * 6.1 Surgical clipping * 6.2 Endovascular coiling * 6.3 Cerebral bypass surgery * 7 Prognosis * 8 Epidemiology * 9 See also * 10 References * 11 External links ## Classification[edit] See also: Aneurysm § Classification Diagram of cerebral aneurysm. Cerebral aneurysms are classified both by size and shape. Small aneurysms have a diameter of less than 15 mm. Larger aneurysms include those classified as large (15 to 25 mm), giant (25 to 50 mm), and super-giant (over 50 mm).[3] ### Saccular aneurysms[edit] Saccular aneurysms, also known as berry aneurysms, appear as a round outpouching and are the most common form of cerebral aneurysm.[3][4] ### Fusiform aneurysms[edit] Fusiform dolichoectatic aneurysms represent a widening of a segment of an artery around the entire blood vessel, rather than just arising from a side of an artery's wall. They can rupture but usually do not.[citation needed] ### Microaneurysms[edit] Main article: Charcot–Bouchard aneurysm Microaneurysms, also known as Charcot–Bouchard aneurysms, typically occur in small blood vessels (less than 300 micrometre diameter), most often the lenticulostriate vessels of the basal ganglia, and are associated with chronic hypertension.[5] Charcot–Bouchard aneurysms are a common cause of intracranial hemorrhage.[citation needed] ## Signs and symptoms[edit] A small, unchanging aneurysm will produce few, if any, symptoms. Before a larger aneurysm ruptures, the individual may experience such symptoms as a sudden and unusually severe headache, nausea, vision impairment, vomiting, and loss of consciousness, or no symptoms at all.[6] ### Subarachnoid bleed[edit] Main article: Subarachnoid hemorrhage § Signs and symptoms If an aneurysm ruptures, blood leaks into the space around the brain. This is called a subarachnoid hemorrhage. Onset is usually sudden without prodrome, classically presenting as a "thunderclap headache" worse than previous headaches.[7][8] Symptoms of a subarachnoid hemorrhage differ depending on the site and size of the aneurysm.[8] Symptoms of a ruptured aneurysm can include: * a sudden severe headache that can last from several hours to days * nausea and vomiting * drowsiness, confusion and/or loss of consciousness * visual abnormalities * meningism Almost all aneurysms rupture at their apex. This leads to hemorrhage in the subarachnoid space and sometimes in brain parenchyma. Minor leakage from aneurysm may precede rupture, causing warning headaches. About 60% of patients die immediately after rupture.[9] Larger aneurysms have a greater tendency to rupture, though most ruptured aneurysms are less than 10 mm in diameter.[8] The risk of a subarachnoid hemorrhage is greater with a saccular aneurysm than a fusiform aneurysm.[10][citation needed] ### Microaneurysms[edit] A ruptured microaneurysm may cause an intracerebral hemorrhage, presenting as a focal neurological deficit.[8] Rebleeding, hydrocephalus (the excessive accumulation of cerebrospinal fluid), vasospasm (spasm, or narrowing, of the blood vessels), or multiple aneurysms may also occur. The risk of rupture from a cerebral aneurysm varies according to the size of an aneurysm, with the risk rising as the aneurysm size increases.[citation needed] ### Vasospasm[edit] See also: Subarachnoid hemorrhage § Vasospasm Vasospasm, referring to blood vessel constriction, can occur secondary to subarachnoid hemorrhage following a ruptured aneurysm. This is most likely to occur within 21 days and is seen radiologically within 60% of such patients. The vasospasm is thought to be secondary to the apoptosis of inflammatory cells such as macrophages and neutrophils that become trapped in the subarachnoid space. These cells initially invade the subarachnoid space from the circulation in order to phagocytose the hemorrhaged red blood cells. Following apoptosis, it is thought there is a massive degranulation of vasoconstrictors, including endothelins and free radicals, that cause the vasospasm.[11] ## Risk factors[edit] Intracranial aneurysms may result from diseases acquired during life, or from genetic conditions. Hypertension, smoking, alcoholism, and obesity are associated with the development of brain aneurysms.[7][8][12] Cocaine use has also been associated with the development of intracranial aneurysms.[8] Other acquired associations with intracranial aneurysms include head trauma and infections.[7] ### Genetic associations[edit] Coarctation of the aorta is also a known risk factor,[7] as is arteriovenous malformation.[9] Genetic conditions associated with connective tissue disease may also be associated with the development of aneurysms.[7] This includes:[13] * autosomal dominant polycystic kidney disease, * neurofibromatosis type I, * Marfan syndrome, * multiple endocrine neoplasia type I, * pseudoxanthoma elasticum, * hereditary hemorrhagic telangiectasia and * Ehlers-Danlos syndrome types II and IV. Specific genes have also had reported association with the development of intracranial aneurysms, including perlecan, elastin, collagen type 1 A2, endothelial nitric oxide synthase, endothelin receptor A and cyclin dependent kinase inhibitor. Mutations in interleukin 6 may be protective.[citation needed]. Recently, several genetic loci have been identified as relevant to the development of intracranial aneurysms. These include 1p34-36, 2p14-15, 7q11, 11q25, and 19q13.1-13.3.[14] ## Pathophysiology[edit] See also: Aneurysm § Pathophysiology Aneurysm means an outpouching of a blood vessel wall that is filled with blood. Aneurysms occur at a point of weakness in the vessel wall. This can be because of acquired disease or hereditary factors. The repeated trauma of blood flow against the vessel wall presses against the point of weakness and causes the aneurysm to enlarge.[15] As described by the law of Young-Laplace, the increasing area increases tension against the aneurysmal walls, leading to enlargement.[citation needed] Both high and low wall shear stress of flowing blood can cause aneurysm and rupture. However, the mechanism of action is still unknown. It is speculated that low shear stress causes growth and rupture of large aneurysms through inflammatory response while high shear stress causes growth and rupture of small aneurysm through mural response (response from the blood vessel wall). Other risk factors that contributes to the formation of aneurysm are: cigarette smoking, hypertension, female gender, family history of cerebral aneurysm, infection, and trauma. Damage to structural integrity of the arterial wall by shear stress causes an inflammatory response with the recruitment of T cells, macrophages, and mast cells. The inflammatory mediators are: interleukin 1 beta, interleukin 6, tumor necrosis factor alpha (TNF alpha), MMP1, MMP2, MMP9, prostaglandin E2, complement system, reactive oxygen species (ROS), and angiotensin II. However, smooth muscle cells from the tunica media layer of the artery moved into the tunica intima, where the function of the smooth muscle cells changed from contractile function into pro-inflammatory function. This causes the fibrosis of the arterial wall, with reduction of number of smooth muscle cells, abnormal collagen synthesis, resulting in a thinning of the arterial wall and the formation of aneurysm and rupture. No specific gene loci has been identified to be associated with cerebral aneurysms.[16] Generally, aneurysms larger than 7 mm in diameter should be treated because they are prone for rupture. Meanwhile, aneurysms less than 7 mm arise from the anterior and posterior communicating artery and are more easily ruptured when compared to aneurysms arising from other locations.[16] ### Saccular aneurysms[edit] The most common sites of intracranial saccular aneurysms Saccular aneurysms are almost always the result of hereditary weaknesses in blood vessels and typically occur within the arteries of the circle of Willis,[15][17] in order of frequency affecting the following arteries:[18] * Anterior communicating artery * Posterior communicating artery * Middle cerebral artery * Internal carotid artery * Tip of basilar artery Saccular aneurysms tend to have a lack of tunica media and elastic lamina around their dilated locations (congenital), with a wall of sac made up of thickened hyalinized intima and adventitia.[9] In addition, some parts of the brain vasculature are inherently weak—particularly areas along the circle of Willis, where small communicating vessels link the main cerebral vessels. These areas are particularly susceptible to saccular aneurysms.[7] Approximately 25% of patients have multiple aneurysms, predominantly when there is a familial pattern.[8] ## Diagnosis[edit] CT angiography showing aneurysm measuring 2.6 mm in diameter at the ACOM (anterior communicating artery). Once suspected, intracranial aneurysms can be diagnosed radiologically using magnetic resonance or CT angiography.[19] But these methods have limited sensitivity for diagnosis of small aneurysms, and often cannot be used to specifically distinguish them from infundibular dilations without performing a formal angiogram.[19][20] The determination of whether an aneurysm is ruptured is critical to diagnosis. Lumbar puncture (LP) is the gold standard technique for determining aneurysm rupture (subarachnoid hemorrhage). Once an LP is performed, the CSF is evaluated for RBC count, and presence or absence of xanthochromia.[21] ## Treatment[edit] A selection of Mayfield and Drake aneurysm clips ready for implantation. Emergency treatment for individuals with a ruptured cerebral aneurysm generally includes restoring deteriorating respiration and reducing intracranial pressure. Currently there are two treatment options for securing intracranial aneurysms: surgical clipping or endovascular coiling. If possible, either surgical clipping or endovascular coiling is typically performed within the first 24 hours after bleeding to occlude the ruptured aneurysm and reduce the risk of rebleeding.[citation needed] While a large meta-analysis found the outcomes and risks of surgical clipping and endovascular coiling to be statistically similar, no consensus has been reached.[22] In particular, the large randomised control trial International Subarachnoid Aneurysm Trial appears to indicate a higher rate of recurrence when intracerebral aneurysms are treated using endovascular coiling. Analysis of data from this trial has indicated a 7% lower eight-year mortality rate with coiling,[23] a high rate of aneurysm recurrence in aneurysms treated with coiling—from 28.6–33.6% within a year,[24][25] a 6.9 times greater rate of late retreatment for coiled aneurysms,[26] and a rate of rebleeding 8 times higher than surgically-clipped aneurysms.[27] ### Surgical clipping[edit] Main article: Surgical clipping Aneurysms can be treated by clipping the base of the aneurysm with a specially-designed clip. Whilst this is typically carried out by craniotomy, a new endoscopic endonasal approach is being trialled.[28] Surgical clipping was introduced by Walter Dandy of the Johns Hopkins Hospital in 1937.[29] After clipping, a catheter angiogram or CTA can be performed to confirm complete clipping.[30] ### Endovascular coiling[edit] Main article: Endovascular coiling Endovascular coiling refers to the insertion of platinum coils into the aneurysm. A catheter is inserted into a blood vessel, typically the femoral artery, and passed through blood vessels into the cerebral circulation and the aneurysm. Coils are pushed into the aneurysm, or released into the blood stream ahead of the aneurysm. Upon depositing within the aneurysm, the coils expand and initiate a thrombotic reaction within the aneurysm. If successful, this prevents further bleeding from the aneurysm.[31] In the case of broad-based aneurysms, a stent may be passed first into the parent artery to serve as a scaffold for the coils.[32] ### Cerebral bypass surgery[edit] Cerebral bypass surgery was developed in the 1960s in Switzerland by Gazi Yasargil. When a patient has an aneurysm involving a blood vessel or a tumor at the base of the skull wrapping around a blood vessel, surgeons eliminate the problem vessel by replacing it with an artery from another part of the body.[33] ## Prognosis[edit] Outcomes depend on the size of the aneurysm.[34] Small aneurysms (less than 7 mm) have a low risk of rupture and increase in size slowly.[34] The risk of rupture is less than one percent for aneurysms of this size.[34] The prognosis for a ruptured cerebral aneurysm depends on the extent and location of the aneurysm, the person's age, general health, and neurological condition. Some individuals with a ruptured cerebral aneurysm die from the initial bleeding. Other individuals with cerebral aneurysm recover with little or no neurological deficit. The most significant factors in determining outcome are the Hunt and Hess grade, and age. Generally patients with Hunt and Hess grade I and II hemorrhage on admission to the emergency room and patients who are younger within the typical age range of vulnerability can anticipate a good outcome, without death or permanent disability. Older patients and those with poorer Hunt and Hess grades on admission have a poor prognosis. Generally, about two-thirds of patients have a poor outcome, death, or permanent disability.[15][35][36] ## Epidemiology[edit] The prevalence of intracranial aneurysm is about 1–5% (10 million to 12 million persons in the United States) and the incidence is 1 per 10,000 persons per year in the United States (approximately 27,000), with 30- to 60-year-olds being the age group most affected.[6][15] Intracranial aneurysms occur more in women, by a ratio of 3 to 2, and are rarely seen in pediatric populations.[6][12] ## See also[edit] * Interventional neuroradiology * Intradural pseudoaneurysm ## References[edit] 1. ^ a b https://www.mayoclinic.org/diseases-conditions/brain-aneurysm/symptoms-causes/syc-20361483 2. ^ https://www.webmd.com/heart-disease/understanding-aneurysm-basics 3. ^ a b "What You Should Know About Cerebral Aneurysms". www.hopkinsmedicine.org. 4. ^ Bhidayasiri, Roongroj; Waters, Michael F.; Giza, Christopher C. (2005). Neurological differential diagnosis : a prioritized approach (3. Dr. ed.). Oxford: Blackwell Publishing. p. 133. ISBN 978-1-4051-2039-5. 5. ^ Kumar; Abbas; Fausto, eds. (2005). Robbins and Cotran Pathologic Basis of Disease (7th ed.). China: Elsevier. ISBN 978-0-7216-0187-8.[page needed] 6. ^ a b c Brisman, JL; Song, JK; Newell, DW (Aug 31, 2006). "Cerebral aneurysms". The New England Journal of Medicine. 355 (9): 928–39. doi:10.1056/nejmra052760. PMID 16943405. 7. ^ a b c d e f Goljan, Edward F. (2006). Rapid Review Pathology (2nd ed.). St. Louis: Mosby. p. 158. ISBN 978-0-323-04414-1. 8. ^ a b c d e f g Alway, David; Cole, John Walden, eds. (2009). Stroke Essentials for Primary Care: A Practical Guide. New York: Humana Press. pp. 86–88, 153. ISBN 978-1-934115-01-5. 9. ^ a b c DiMaio, Vincent J.; DiMaio, Dominick (2001). Forensic pathology (2nd ed.). Boca Raton, FL: CRC Press. p. 61. ISBN 978-0-8493-0072-1. 10. ^ "Cerebral Aneurysm". Columbia University Department of Neurology. Retrieved 10 May 2020. 11. ^ Gallia, Gary L.; Tamargo, Rafael J. (1 October 2006). "Leukocyte-endothelial cell interactions in chronic vasospasm after subarachnoid hemorrhage". Neurological Research. 28 (7): 750–58. doi:10.1179/016164106X152025. PMID 17164038. S2CID 27713975. 12. ^ a b Brown, Walter L. Kemp, Dennis K. Burns, Travis G. (2008). Pathology the big picture. New York: McGraw-Hill Medical. p. 148. ISBN 978-0-07-159379-3. 13. ^ Caranci, F.; Briganti, F.; Cirillo, L.; Leonardi, M.; Muto, M. (2012). "Epidemiology and genetics of intracranial aneurysms". European Journal of Radiology. 82 (10): 1598–605. doi:10.1016/j.ejrad.2012.12.026. PMID 23399038. 14. ^ van der Voet, M; Olson, J; Kuivaniemi, H; Dudek, D; Skunca, M; Ronkainen, A; Niemelä, M; Jääskeläinen, J; Hernesniemi, J; Helin, K (1 March 2004). "Intracranial Aneurysms in Finnish Families: Confirmation of Linkage and Refinement of the Interval to Chromosome 19q13.3". The American Journal of Human Genetics. 74 (3): 564–71. doi:10.1086/382285. PMC 1182270. PMID 14872410. 15. ^ a b c d Haberland, Catherine (2007). Clinical neuropathology : text and color atlas ([Online-Ausg.]. ed.). New York: Demos. p. 70. ISBN 978-1-888799-97-2. 16. ^ a b Chalouhi, Nohra; Loh, Brian L; Hasan, David (25 November 2013). "Review of Cerebral Aneurysm Formation, Growth, and Rupture". Stroke. 44 (12): 3613–22. doi:10.1161/STROKEAHA.113.002390. PMID 24130141. 17. ^ "berry aneurysm" at Dorland's Medical Dictionary 18. ^ Howlett, David; Ayers, Brian (2004). The hands-on guide to imaging. Oxford: Blackwell. pp. 204. ISBN 978-1-4051-1551-3. 19. ^ a b White, Philip M.; Teasdale, Evelyn M.; Wardlaw, Joanna M.; Easton, Valerie (2001-06-01). "Intracranial Aneurysms: CT Angiography and MR Angiography for Detection – Prospective Blinded Comparison in a Large Patient Cohort". Radiology. 219 (3): 739–49. doi:10.1148/radiology.219.3.r01ma16739. ISSN 0033-8419. PMID 11376263. 20. ^ Greenberg, Mark (2010). Handbook of neurosurgery. Greenberg Graphics. ISBN 978-1604063264. OCLC 892183792.[page needed] 21. ^ Mark, Dustin G.; Kene, Mamata V.; Offerman, Steven R.; Vinson, David R.; Ballard, Dustin W. (2015). "Validation of cerebrospinal fluid findings in aneurysmal subarachnoid hemorrhage". The American Journal of Emergency Medicine. 33 (9): 1249–52. doi:10.1016/j.ajem.2015.05.012. PMID 26022754. 22. ^ Raja, PV; Huang, J; Germanwala, AV; Gailloud, P; Murphy, KP; Tamargo, RJ (June 2008). "Microsurgical clipping and endovascular coiling of intracranial aneurysms: a critical review of the literature". Neurosurgery. 62 (6): 1187–202, discussion 1202–03. doi:10.1227/01.neu.0000333291.67362.0b. PMID 18824986. 23. ^ Mitchell P, Kerr R, Mendelow AD, Molyneux A. "Could late rebleeding overturn the superiority of cranial aneurysm coil embolization over clip ligation seen in ISAT?" Journal of Neurosurgery 108: 437–42, March 2008 24. ^ Piotin, M; Spelle, L; Mounayer, C; Salles-Rezende, MT; Giansante-Abud, D; Vanzin-Santos, R; Moret, J (May 2007). "Intracranial aneurysms: treatment with bare platinum coils – aneurysm packing, complex coils, and angiographic recurrence". Radiology. 243 (2): 500–08. doi:10.1148/radiol.2431060006. PMID 17293572. 25. ^ Raymond, J; Guilbert, F; Weill, A; Georganos, SA; Juravsky, L; Lambert, A; Lamoureux, J; Chagnon, M; Roy, D (June 2003). "Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils". Stroke. 34 (6): 1398–1403. doi:10.1161/01.STR.0000073841.88563.E9. PMID 12775880. 26. ^ Campi A, Ramzi N, Molyneux AJ, Summers PE, Kerr RS, Sneade M, Yarnold JA, Rischmiller J, Byrne JV (May 2007). "Retreatment of ruptured cerebral aneurysms in patients randomized by coiling or clipping in the International Subarachnoid Aneurysm Trial (ISAT)". Stroke. 38 (5): 1538–44. doi:10.1161/STROKEAHA.106.466987. PMID 17395870. 27. ^ Mitchell P, Kerr R, Mendelow AD, Molyneux A (March 2008). "Could late rebleeding overturn the superiority of cranial aneurysm coil embolization over clip ligation seen in the International Subarachnoid Aneurysm Trial?". J. Neurosurg. 108 (3): 437–42. doi:10.3171/JNS/2008/108/3/0437. PMID 18312088. S2CID 24304414. 28. ^ "Germanwala Presents First Aneurysm Patient Treated Through Nose". UNC. June 25, 2009. 29. ^ Sasidharan, Gopalakrishnan Madhavan; Sastri, Savitr B V; Pandey, Paritosh (1 January 2015). "Aneurysm clips: What every resident should know". Neurology India. 63 (1) – via www.neurologyindia.com. 30. ^ Bharatha A, Yeung R, Durant D, Fox AJ, Aviv RI, Howard P, Thompson AL, Bartlett ES, Symons SP. "Comparison of computed tomography angiography with digital subtraction angiography in the assessment of clipped intracranial aneurysms". Journal of Computer Assisted Tomography. 2010 May–June; 34(3): 440–45. 31. ^ Brilstra EH, Rinkel GJ, van der Graaf Y, van Rooij WJ, Algra A (February 1999). "Treatment of intracranial aneurysms by embolization with coils: a systematic review". Stroke. 30 (2): 470–76. doi:10.1161/01.STR.30.2.470. PMID 9933290. 32. ^ Oushy, Soliman; Rinaldo, Lorenzo; Brinjikji, Waleed; Cloft, Harry; Lanzino, Giuseppe (June 2020). "Recent advances in stent-assisted coiling of cerebral aneurysms". Expert Review of Medical Devices. 17 (6): 519–32. doi:10.1080/17434440.2020.1778463. ISSN 1745-2422. PMID 32500761. S2CID 219328499. 33. ^ Spetzler, Robert; Chater, Norman (1 November 1976). "Microvascular bypass surgery". Journal of Neurosurgery. 45 (5): 508–13. doi:10.3171/jns.1976.45.5.0508. PMID 972334. 34. ^ a b c Malhotra A, Wu X, Forman HP, Grossetta Nardini HK, Matouk CC, Gandhi D, Moore C, Sanelli P (July 2017). "Growth and Rupture Risk of Small Unruptured Intracranial Aneurysms: A Systematic Review". Ann. Intern. Med. 167 (1): 26–33. doi:10.7326/M17-0246. PMID 28586893. 35. ^ Hop, J. W.; Rinkel, G. J.E.; Algra, A.; van Gijn, J. (1 March 1997). "Case-Fatality Rates and Functional Outcome After Subarachnoid Hemorrhage : A Systematic Review". Stroke. 28 (3): 660–64. doi:10.1161/01.STR.28.3.660. PMID 9056628. 36. ^ Ljunggren, B; Sonesson, B; Säveland, H; Brandt, L (May 1985). "Cognitive impairment and adjustment in patients without neurological deficits after aneurysmal SAH and early operation". Journal of Neurosurgery. 62 (5): 673–79. doi:10.3171/jns.1985.62.5.0673. PMID 3989590. S2CID 26649695. ## External links[edit] Wikimedia Commons has media related to Cerebral aneurysms. * National Institute of Neurological Disorders and Stroke Classification D * ICD-10: I67.1 * ICD-9-CM: 437.3 * MeSH: D002532 * SNOMED CT: 128609009 External resources * MedlinePlus: 001414 * v * t * e Cerebrovascular diseases including stroke Ischaemic stroke Brain * Anterior cerebral artery syndrome * Middle cerebral artery syndrome * Posterior cerebral artery syndrome * Amaurosis fugax * Moyamoya disease * Dejerine–Roussy syndrome * Watershed stroke * Lacunar stroke Brain stem * Brainstem stroke syndrome * Medulla * Medial medullary syndrome * Lateral medullary syndrome * Pons * Medial pontine syndrome / Foville's * Lateral pontine syndrome / Millard-Gubler * Midbrain * Weber's syndrome * Benedikt syndrome * Claude's syndrome Cerebellum * Cerebellar stroke syndrome Extracranial arteries * Carotid artery stenosis * precerebral * Anterior spinal artery syndrome * Vertebrobasilar 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this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Intracranial aneurysm	c0007766	3,906	wikipedia	https://en.wikipedia.org/wiki/Intracranial_aneurysm	2021-01-18T19:03:38	{"mesh": ["D002532"], "umls": ["C0007766"], 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Psychiatrist Aaron T. Beck who laid the groundwork for research on cognitive distortion. An exaggerated or irrational thought pattern involved in the onset or perpetuation of psychopathological states A cognitive distortion is an exaggerated or irrational thought pattern involved in the onset or perpetuation of psychopathological states, such as depression and anxiety.[1] Psychiatrist Aaron T. Beck laid the groundwork for the study of these distortions, and his student David D. Burns continued research on the topic. In his book Feeling Good: The New Mood Therapy, Burns described personal and professional anecdotes related to cognitive distortions and their elimination.[2] Cognitive distortions are thoughts that cause individuals to perceive reality inaccurately. According to Beck's cognitive model, a negative outlook on reality, sometimes called negative schemas (or schemata), is a factor in symptoms of emotional dysfunction and poorer subjective well-being. Specifically, negative thinking patterns reinforce negative emotions and thoughts.[3] During difficult circumstances, these distorted thoughts can contribute to an overall negative outlook on the world and a depressive or anxious mental state. According to hopelessness theory and Beck's theory, the meaning or interpretation that people give to their experience importantly influences whether they will become depressed and whether they will suffer severe, repeated, or long-duration episodes of depression.[4] Challenging and changing cognitive distortions is a key element of cognitive behavioral therapy (CBT). ## Contents * 1 Definition * 2 History * 3 Main types * 3.1 All-or-nothing thinking * 3.2 Overgeneralizing * 3.3 Filtering * 3.4 Disqualifying the positive * 3.5 Jumping to conclusions * 3.6 Magnification and minimization * 3.7 Emotional reasoning * 3.8 Making "must" or "should" statements * 3.9 Personalization and blaming * 3.10 Always being right * 3.11 Fallacy of change * 3.12 Fallacy of fairness * 3.13 Labeling and mislabeling * 4 Conceptualization * 5 Cognitive restructuring * 6 Narcissistic defense * 7 Decatastrophizing * 8 Criticism * 9 See also * 10 References ## Definition[edit] Cognitive comes from the Medieval Latin cognitīvus, equivalent to Latin cognit(us), 'known'.[5] Distortion means the act of twisting or altering something out of its true, natural, or original state.[6] ## History[edit] In 1957 Albert Ellis, though he did not know it yet, would aid cognitive therapy in correcting cognitive distortions and indirectly helping David D. Burns in writing The Feeling Good Handbook. Ellis created what he called the ABC Technique of rational beliefs. The ABC stands for the activating event, beliefs that are irrational, and the consequences that come from the belief. Ellis wanted to prove that the activating event is not what caused the emotional behavior or the consequences, but the beliefs and how the person irrationally perceive the events that aids the consequences.[7] With this model, Ellis attempted to use rational emotive behavior therapy (REBT) with his patients, in order to help them "reframe" or reinterpret the experience in a more rational manner. In this model Ellis explains it all for his clients, while Beck helps his clients figure this out on their own.[8] Beck first started to notice these automatic distorted thought processes when practicing psychoanalysis, while his patients followed the rule of saying anything that comes to mind. Aaron realized that his patients had irrational fears, thoughts, and perceptions that were automatic. Beck began noticing his automatic thought processes that he knew his patients had but did not report. Most of the time the thoughts were biased against themselves and very erroneous.[9] Beck believed that the negative schemas developed and manifested themselves in the perspective and behavior. The distorted thought processes lead to focusing on degrading the self, amplifying minor external setbacks, experiencing other's harmless comments as ill-intended, while simultaneously seeing self as inferior. Inevitably cognitions are reflected in their behavior with a reduced desire to care for oneself, to seek pleasure, and give up. These exaggerated perceptions, due to cognition, feel real and accurate because the schemas, after being reinforced through the behavior, tend to become automatic and do not allow time for reflection.[10] This cycle is also known as Beck's cognitive triad, focused on the theory that the person's negative schema applied to the self, the future, and the environment.[11] In 1972, psychiatrist, psychoanalyst, and cognitive therapy scholar Aaron T. Beck published Depression: Causes and Treatment.[12] He was dissatisfied with the conventional Freudian treatment of depression, because there was no empirical evidence for the success of Freudian psychoanalysis. Beck's book provided a comprehensive and empirically-supported theoretical model for depression—its potential causes, symptoms, and treatments. In Chapter 2, titled "Symptomatology of Depression", he described "cognitive manifestations" of depression, including low self-evaluation, negative expectations, self-blame and self-criticism, indecisiveness, and distortion of the body image.[12] When Burns published Feeling Good: The New Mood Therapy, it made Beck's approach to distorted thinking widely known and popularized.[13][14] Burns sold over four million copies of the book in the United States alone. It was a book commonly "prescribed" for patients who have cognitive distortions that have led to depression. Beck approved of the book, saying that it would help others alter their depressed moods by simplifying the extensive study and research that had taken place since shortly after Beck had started as a student and practitioner of psychoanalytic psychiatry. Nine years later The Feeling Good Handbook was published, which was also built on Beck's work and includes a list of ten specific cognitive distortions that will be discussed throughout this article.[15] ## Main types[edit] Examples of some common cognitive distortions seen in depressed and anxious individuals. People may be taught how to identify and alter these distortions as part of cognitive behavioural therapy. The cognitive distortions listed below[15] are categories of automatic thinking, and are to be distinguished from logical fallacies.[16] ### All-or-nothing thinking[edit] Main article: Splitting (psychology) The "all-or-nothing thinking distortion" is also referred to as “splitting,"[17] “black-and-white thinking,"[3] and "polarized thinking."[18] Someone with the all-or-nothing thinking distortion looks at life in black and white categories.[15] Either they are a success or a failure; either they are good or bad; there is no in-between. According to one article, “Because there is always someone who is willing to criticize, this tends to collapse into a tendency for polarized people to view themselves as a total failure. Polarized thinkers have difficulty with the notion of being ‘good enough’ or a partial success."[17] * Example (from The Feeling Good Handbook): A woman eats a spoonful of ice cream. She thinks she is a complete failure for breaking her diet. She becomes so depressed that she ends up eating the whole quart of ice cream.[15] This example captures the polarized nature of this distortion—the person believes they are totally inadequate if they fall short of perfection. In order to combat this distortion, Burns suggests thinking of the world in terms of shades of gray.[15] Rather than viewing herself as a complete failure for eating a spoonful of ice cream, the woman in the example could still recognize her overall effort to diet as at least a partial success. This distortion is commonly found in perfectionists.[13] ### Overgeneralizing[edit] Someone who overgeneralizes makes hasty generalizations from insufficient evidence. Such as seeing a “single negative event” as a “never-ending pattern of defeat,"[15] and as such drawing a very broad conclusion from a single incident or a single piece of evidence. Even if something bad happens only once, it is expected to happen over and over again.[3] * Example 1: A young woman is asked out on a first date, but not a second one. She is distraught as she tells her friend, “This always happens to me! I’ll never find love!” * Example 2: A woman is lonely and often spends most of her time at home. Her friends sometimes ask her to dinner and to meet new people. She feels it is useless to even try. No one really could like her. And anyway, all people are the same; petty and selfish.[19] One suggestion to combat this distortion is to “examine the evidence” by performing an accurate analysis of one's situation. This aids in avoiding exaggerating one's circumstances.[15] ### Filtering[edit] Filtering distortions occur when an individual dwells only on the negative details of a situation and filters out the positive aspects.[15] * Example: Andy gets mostly compliments and positive feedback about a presentation he has done at work, but he also has received a small piece of criticism. For several days following his presentation, Andy dwells on this one negative reaction, forgetting all of the positive reactions that he had also been given.[15] The Feeling Good Handbook notes that filtering is like a “drop of ink that discolors a beaker of water."[15] One suggestion to combat filtering is a cost–benefit analysis. A person with this distortion may find it helpful to sit down and assess whether filtering out the positive and focusing on the negative is helping or hurting them in the long run.[15] ### Disqualifying the positive[edit] Disqualifying the positive refers to rejecting positive experiences by insisting they "don't count" for some reason or other. Negative belief is maintained despite contradiction by everyday experiences. Disqualifying the positive may be the most common fallacy in the cognitive distortion range; it is often analyzed with "always being right", a type of distortion where a person is in an all-or-nothing self-judgment. People in this situation show signs of depression. Examples include: * "I will never be as good as Jane" * "Anyone could have done as well"[15] * "They are just congratulating me to be nice"[20] ### Jumping to conclusions[edit] Main article: Jumping to conclusions Reaching preliminary conclusions (usually negative) with little (if any) evidence. Two specific subtypes are identified: * Mind reading: Inferring a person's possible or probable (usually negative) thoughts from his or her behavior and nonverbal communication; taking precautions against the worst suspected case without asking the person. * Example 1: A student assumes that the readers of his or her paper have already made up their minds concerning its topic, and, therefore, writing the paper is a pointless exercise.[16] * Example 2: Kevin assumes that because he sits alone at lunch, everyone else must think he is a loser. (This can encourage self-fulfilling prophecy; Kevin may not initiate social contact because of his fear that those around him already perceive him negatively).[21] * Fortune-telling: Predicting outcomes (usually negative) of events. * Example: A depressed person tells themselves they will never improve; they will continue to be depressed for their whole life.[15] One way to combat this distortion is to ask, “If this is true, does it say more about me or them?"[22] ### Magnification and minimization[edit] Main articles: Exaggeration and Minimisation (psychology) Giving proportionally greater weight to a perceived failure, weakness or threat, or lesser weight to a perceived success, strength or opportunity, so that the weight differs from that assigned by others, such as "making a mountain out of a molehill". In depressed clients, often the positive characteristics of other people are exaggerated and their negative characteristics are understated. * Catastrophizing – Giving greater weight to the worst possible outcome, however unlikely, or experiencing a situation as unbearable or impossible when it is just uncomfortable. ### Emotional reasoning[edit] Main article: Emotional reasoning In the emotional reasoning distortion, it is assumed that feelings expose the true nature of things and experience reality as a reflection of emotionally linked thoughts; something is believed true solely based on a feeling. * Examples: "I feel stupid, therefore I must be stupid".[3] Feeling fear of flying in planes, and then concluding that planes must be a dangerous way to travel.[15] Feeling overwhelmed by the prospect of cleaning one's house, therefore concluding that it's hopeless to even start cleaning.[19] ### Making "must" or "should" statements[edit] Making "must" or "should" statements was included by Albert Ellis in his rational emotive behavior therapy (REBT), an early form of CBT; he termed it "musturbation". Michael C. Graham called it "expecting the world to be different than it is".[23] It can be seen as demanding particular achievements or behaviors regardless of the realistic circumstances of the situation. * Example: After a performance, a concert pianist believes he or she should not have made so many mistakes.[19] * In Feeling Good: The New Mood Therapy, David Burns clearly distinguished between pathological "should statements", moral imperatives, and social norms. A related cognitive distortion, also present in Ellis' REBT, is a tendency to "awfulize"; to say a future scenario will be awful, rather than to realistically appraise the various negative and positive characteristics of that scenario. According to Burns, “must" and “should” statements are negative because they cause the person to feel guilty and upset at themselves. Some people also direct this distortion at other people, which can cause feelings of anger and frustration when that other person does not do what they should have done. He also mentions how this type of thinking can lead to rebellious thoughts. In other words, trying to whip oneself into doing something with “shoulds” may cause one to desire just the opposite.[15] ### Personalization and blaming[edit] Main article: Blame Personalization is assigning personal blame disproportionate to the level of control a person realistically has in a given situation. * Example 1: A foster child assumes that he/she has not been adopted because he/she is not “loveable enough.” * Example 2: A child has bad grades. His/her mother believes it is because she is not a good enough parent.[15] Blaming is the opposite of personalization. In the blaming distortion, the disproportionate level of blame is placed upon other people, rather than oneself.[15] In this way, the person avoids taking personal responsibility, making way for a “victim mentality.” * Example: Placing blame for marital problems entirely on one's spouse.[15] ### Always being right[edit] In this cognitive distortion, being wrong is unthinkable. This distortion is characterized by actively trying to prove one's actions or thoughts to be correct, and sometimes prioritizing self-interest over the feelings of another person.[3] In this cognitive distortion, the facts that oneself has about their surroundings are always right while other people's opinions and perspectives are wrongly seen.[24] ### Fallacy of change[edit] Relying on social control to obtain cooperative actions from another person.[3] The underlying assumption of this thinking style is that one's happiness depends on the actions of others. The fallacy of change also assumes that other people should change to suit one's own interests automatically and/or that it is fair to pressure them to change. It may be present in most abusive relationships in which partners' "visions" of each other are tied into the belief that happiness, love, trust, and perfection would just occur once they or the other person change aspects of their beings.[25] ### Fallacy of fairness[edit] Fallacy of fairness is the belief that life should be fair. When life is perceived to be unfair, an angry emotional state is produced which may lead to attempts to correct the situation.[3] There are few situations in which "universal justice" can be applied or excluded. Justice comes from the late Old English justice ‘administration of the law’, fairness and justice vary between culture, people, or country, it is seen that they need to be attributed in any situation.[26] ### Labeling and mislabeling[edit] Main article: Labeling theory A form of overgeneralization; attributing a person's actions to his or her character instead of to an attribute. Rather than assuming the behaviour to be accidental or otherwise extrinsic, one assigns a label to someone or something that is based on the inferred character of that person or thing. ## Conceptualization[edit] In a series of publications,[27][28][29] philosopher Paul Franceschi has proposed a unified conceptual framework for cognitive distortions designed to clarify their relationships and define new ones. This conceptual framework is based on three notions: (i) the reference class (a set of phenomena or objects, e.g. events in the patient's life); (ii) dualities (positive/negative, qualitative/quantitative, ...); the taxon system (degrees allowing to attribute properties according to a given duality to the elements of a reference class). In this model, "dichotomous reasoning", "minimization", "maximization" and "arbitrary focus" constitute general cognitive distortions (applying to any duality), whereas "disqualification of the positive" and "catastrophism" are specific cognitive distortions, applying to the positive/negative duality. This conceptual framework posits two additional cognitive distortion classifications: the "omission of the neutral" and the "requalification in the other pole". ## Cognitive restructuring[edit] Cognitive restructuring (CR) is a popular form of therapy used to identify and reject maladaptive cognitive distortions,[30] and is typically used with individuals diagnosed with depression.[31] In CR, the therapist and client first examine a stressful event or situation reported by the client. For example, a depressed male college student who experiences difficulty in dating might believe that his "worthlessness" causes women to reject him. Together, therapist and client might then create a more realistic cognition, e.g., "It is within my control to ask girls on dates. However, even though there are some things I can do to influence their decisions, whether or not they say yes is largely out of my control. Thus, I am not responsible if they decline my invitation." CR therapies are designed to eliminate "automatic thoughts" that include clients' dysfunctional or negative views. According to Beck, doing so reduces feelings of worthlessness, anxiety, and anhedonia that are symptomatic of several forms of mental illness.[32] CR is the main component of Beck's and Burns's CBT.[33] ## Narcissistic defense[edit] Main article: Narcissistic defences Those diagnosed with narcissistic personality disorder tend to view themselves as unrealistically superior and overemphasize their strengths but understate their weaknesses.[32] As such, narcissists use exaggeration and minimization to defend against psychic pain.[34][35] ## Decatastrophizing[edit] Main article: Decatastrophizing In cognitive therapy, decatastrophizing or decatastrophization is a cognitive restructuring technique that may be used to treat cognitive distortions, such as magnification and catastrophizing,[36] commonly seen in psychological disorders like anxiety[31] and psychosis.[37] Major features of these disorders are the subjective report of being overwhelmed by life circumstances and the incapability of affecting them. The goal of CR is to help the client change his or her perceptions to render the felt experience as less significant. ## Criticism[edit] Main article: Cognitive behavioral therapy § Criticisms Common criticisms of the diagnosis of cognitive distortion relate to epistemology and the theoretical basis. If the perceptions of the patient differ from those of the therapist, it may not be because of intellectual malfunctions but because the patient has different experiences. In some cases, depressed subjects appear to be “sadder but wiser”.[38] ## See also[edit] * Cognitive bias – Systematic pattern of deviation from norm or rationality in judgment * Cognitive dissonance – Psychological stress resulting from multiple contradictory beliefs, ideas, or values held at the same time * Defence mechanism – Unconscious psychological mechanism that reduces anxiety arising from unacceptable or potentially harmful stimuli * Destabilisation * Dysfunctional belief * Emotion and memory – Critical factors contributing to the emotional enhancement effect on human memory * Gaslighting – Form of psychological manipulation * Illusion – Distortion of the perception of reality * Language and thought * List of cognitive biases – Systematic patterns of deviation from norm or rationality in judgment * List of fallacies – Types of reasoning that are logically incorrect * Negativity bias * Parataxic distortion * Rationalization (psychology) ## References[edit] 1. ^ Helmond, Petra; Overbeek, Geertjan; Brugman, Daniel; Gibbs, John C. (2015). "A Meta-Analysis on Cognitive Distortions and Externalizing Problem Behavior" (PDF). Criminal Justice and Behavior. 42 (3): 245–262. doi:10.1177/0093854814552842. S2CID 146611029. 2. ^ Burns, David D. (1980). Feeling Good: The New Mood Therapy. 3. ^ a b c d e f g Grohol, John (2009). "15 Common Cognitive Distortions". PsychCentral. Archived from the original on 2009-07-07.CS1 maint: bot: original URL status unknown (link) 4. ^ "APA PsycNet". psycnet.apa.org. Retrieved 2020-06-29. 5. ^ "Cognitive". Dictionary.com Unabridged. Random House. Retrieved 2020-03-14. 6. ^ "Distortion". Merriam-Webster Dictionary. Retrieved 2020-03-14. 7. ^ McLeod, Saul A. "Cognitive Behavioral Therapy". SimplyPsychology. 8. ^ Ellis, Albert (1957). "Rational Psychotherapy and Individual Psychology". Journal of Individual Psychology. 13: 42. 9. ^ Beck, Aaron T. (1997). "The Past and Future of Cognitive Therapy". Journal of Psychotherapy and Research. 6 (4): 277. PMC 3330473. PMID 9292441. 10. ^ Kovacs, Maria; Beck, Aaron T. (1986). "Maladaptive Cognitive Structure in Depression". The American Journal of Psychiatry: 526. 11. ^ Beck, Aaron T. (1967). Depression Causes and Treatment. Philadelphia, Pennsylvania: University of Pennsylvania Press. p. 166. 12. ^ a b Beck, Aaron T. (1972). Depression; Causes and Treatment. Philadelphia: University of Pennsylvania Press. ISBN 978-0-8122-7652-7. 13. ^ a b Burns, David D. (1980). Feeling Good: The New Mood Therapy. New York: Morrow. ISBN 978-0-688-03633-1. 14. ^ Roberts, Joe. "History of Cognitive Behavioral Therapy". National Association of Cognitive Behavioral Therapists Online Headquarters. National Association of Cognitive Behavioral Therapists. Archived from the original on 2016-05-06. Retrieved 9 April 2020. 15. ^ a b c d e f g h i j k l m n o p q r Burns, David D. (1980). The Feeling Good Handbook: Using the New Mood Therapy in Everyday Life. New York: W. Morrow. ISBN 978-0-688-01745-3. 16. ^ a b Tagg, John (1996). "Cognitive Distortions". Archived from the original on November 1, 2011. Retrieved October 24, 2011. 17. ^ a b "Cognitive Distortions Affecting Stress". MentalHelp.net. Retrieved 8 April 2020. 18. ^ Grohol, John M. (17 May 2016). "15 Common Cognitive Distortions". PsychCentral. Retrieved 8 April 2020. 19. ^ a b c Schimelpfening, Nancy. "You Are What You Think". 20. ^ "Disqualifying the Positive". Palomar. Retrieved 2020-01-03. 21. ^ "Cognitive Distortions: Jumping to Conclusions & All or Nothing Thinking". Moodfit. Retrieved 9 April 2020. 22. ^ "Common Cognitive Distortions: Mind Reading". Cognitive Behavioral Therapy - Los Angeles. Retrieved 8 April 2020. 23. ^ Graham, Michael C. (2014). Facts of Life: ten issues of contentment. Outskirts Press. p. 37. ISBN 978-1-4787-2259-5. 24. ^ "15 Common Cognitive Distortions". PsychCentral. 2016-05-17. Retrieved 2020-02-28. 25. ^ "Fallacy of Change: 15 types of distorted thinking that lead to massive anxiety 10/15". Abate Counseling. 2018-08-30. 26. ^ "Fallacy of Change: 15 types of distorted thinking that lead to massive anxiety 10/15". Real Clear Politics. 27. ^ Franceschi, Paul (2007). "Compléments pour une théorie des distorsions cognitives". Journal de Thérapie Comportementale et Cognitive. 17 (2): 84–88. doi:10.1016/s1155-1704(07)89710-2. 28. ^ Franceschi, Paul (2009). "Théorie des distorsions cognitives : la sur-généralisation et l'étiquetage". Journal de Thérapie Comportementale et Cognitive. 19 (4): 136–140. doi:10.1016/j.jtcc.2009.10.003. 29. ^ Franceschi, Paul (2010). "Théorie des distorsions cognitives : la personnalisation". Journal de Thérapie Comportementale et Cognitive. 20 (2): 51–55. doi:10.1016/j.jtcc.2010.06.006. 30. ^ Gil, Pedro J. Moreno; Carrillo, Francisco Xavier Méndez; Meca, Julio Sánchez (2001). "Effectiveness of cognitive-behavioural treatment in social phobia: A meta-analytic review". Psychology in Spain. 5: 17–25. S2CID 8860010. 31. ^ a b Martin, Ryan C.; Dahlen, Eric R. (2005). "Cognitive emotion regulation in the prediction of depression, anxiety, stress, and anger". Personality and Individual Differences. 39 (7): 1249–1260. doi:10.1016/j.paid.2005.06.004. 32. ^ a b Diagnostic and statistical manual of mental disorders : DSM-5. American Psychiatric Association., American Psychiatric Association. DSM-5 Task Force. (5th ed.). Arlington, VA: American Psychiatric Association. 2013. ISBN 9780890425541. OCLC 830807378.CS1 maint: others (link) 33. ^ Rush, A.; Khatami, M.; Beck, A. (1975). "Cognitive and Behavior Therapy in Chronic Depression". Behavior Therapy. 6 (3): 398–404. doi:10.1016/S0005-7894(75)80116-X. 34. ^ Millon, Theodore; Carrie M. Millon; Seth Grossman; Sarah Meagher; Rowena Ramnath (2004). Personality Disorders in Modern Life. John Wiley and Sons. ISBN 978-0-471-23734-1. 35. ^ Thomas, David (2010). Narcissism: Behind the Mask. ISBN 978-1-84624-506-0. 36. ^ Theunissen, Maurice; Peters, Madelon L.; Bruce, Julie; Gramke, Hans-Fritz; Marcus, Marco A. (2012). "Preoperative Anxiety and Catastrophizing". The Clinical Journal of Pain. 28 (9): 819–841. doi:10.1097/ajp.0b013e31824549d6. PMID 22760489. S2CID 12414206. 37. ^ Moritz, Steffen; Schilling, Lisa; Wingenfeld, Katja; Köther, Ulf; Wittekind, Charlotte; Terfehr, Kirsten; Spitzer, Carsten (2011). "Persecutory delusions and catastrophic worry in psychosis: Developing the understanding of delusion distress and persistence". Journal of Behavior Therapy and Experimental Psychiatry. 42 (September 2011): 349–354. doi:10.1016/j.jbtep.2011.02.003. PMID 21411041. 38. ^ Beidel, Deborah C. (1986). "A Critique of the Theoretical Bases of Cognitive Behavioral Theories and Therapy". Clinical Psychology Review. 6 (2): 177–97. doi:10.1016/0272-7358(86)90011-5. * v * t * e Defence mechanisms Level 1: Pathological * Delusional projection * Denial or abnegation (German: Verneinung) * Psychotic denial or disavowal (German: Verleugnung) * Distortion * Foreclosure or repudiation (German: Verwerfung) * Extreme projection * Identification with the Aggressor * Splitting Level 2: Immature * Acting out * Fantasy * Idealization * Introjection * Passive-aggression * Projection * Projective identification * Somatization Level 3: Neurotic * Displacement * Dissociation * Hypochondriasis * Intellectualization * Isolation * Rationalization * Reaction formation * Regression * Repression (German: Verdrängung) * Undoing Level 4: Mature * Altruism * Anticipation * Humour * Identification * Sublimation * Suppression Other mechanisms * Compartmentalization * Defensive pessimism * Exaggeration * Minimisation * Postponement of affect See also * Narcissistic defences * Censorship (psychoanalysis) [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Cognitive distortion	None	3,907	wikipedia	https://en.wikipedia.org/wiki/Cognitive_distortion	2021-01-18T19:05:01	{"wikidata": ["Q2914540"]}
Lymphatic filariasis (LF) is a severe form of filariasis (see this term), caused by the parasitic worms Wuchereria bancrofti, Brugia malayi and Brugia timori, and the most common cause of acquired lymphedema worldwide. LF is endemic to tropical and subtropical regions. The vast majority of infected patients are asymptomatic but it can also cause a variety of clinical manifestations, including limb lymphedema, genital anomalies (hydrocele, chylocele), elephantiasis in later stages of the disease (frequently in the lower extremities), and tropical pulmonary eosinophilia (nocturnal paroxysmal cough and wheezing, weight loss, low-grade fever, adenopathy, and pronounced blood eosinophilia). Renal involvement (hematuria, proteinuria, nephritic syndrome, glomerulonephritis), and mono-arthritis of the knee or ankle joint have 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	Lymphatic filariasis	c0013884	3,908	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2035	2021-01-23T17:27:27	{"gard": ["3321"], "mesh": ["D004605"], "umls": ["C0013884"], "icd-10": ["B74.0", "B74.1", "B74.2"]}
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1NN (CMD1NN) is caused by heterozygous mutation in the RAF1 gene (164760) on chromosome 3p25. For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200). Clinical Features Dhandapany et al. (2014) reported patients with nonsyndromic dilated cardiomyopathy (CMD) and mutations in the RAF1 gene (see MOLECULAR GENETICS). Of 10 patients in whom age of onset was known, 8 presented in childhood or adolescence. The average age at presentation was 12.6 years, which the authors noted was younger than the approximate average of 20 years associated with CMD caused by sarcomeric gene mutations. Molecular Genetics In 218 patients from South India with nonsyndromic dilated cardiomyopathy, Dhandapany et al. (2014) analyzed 9 RAS-MAPK genes and identified 4 heterozygous mutations in the RAF1 gene (see, e.g., 164760.0005 and 164760.0006) in 5 of the CMD probands. The RAF1 mutations were not found in 500 ancestry-matched controls or in 13,600 European and African American alleles in the Exome Sequencing Project database; in addition, the 5 probands were negative for mutation in 12 known cardiomyopathy genes. Dhandapany et al. (2014) screened 200 North Indian, 35 Japanese, and 60 Italian probands with CMD for mutations in RAF1 and identified 2 different heterozygous mutations in 2 North Indian patients (see, e.g., 164760.0006) and 2 in 2 Japanese patients (see, e.g., 164760.0007). INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Dilated cardiomyopathy \- Decreased left ventricular ejection fraction \- Mitral regurgitation, mild to severe \- Ventricular arrhythmia (in some patients) MISCELLANEOUS \- Onset in childhood or adolescence in most patients MOLECULAR BASIS \- Caused by mutation in the v-raf-1 murine leukemia viral oncogene homolog-1 gene (RAF1, 164760.0005 ) ▲ 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	CARDIOMYOPATHY, DILATED, 1NN	c0340427	3,909	omim	https://www.omim.org/entry/615916	2019-09-22T15:50:34	{"doid": ["0110432"], "mesh": ["C536231"], "omim": ["615916"], "orphanet": ["154"]}
Q fever is a worldwide disease with acute and chronic stages caused by the bacteria known as Coxiella burnetii. Cattle, sheep, and goats are the primary reservoirs although a variety of species may be infected. Organisms are excreted in birth fluids, milk, urine, and feces of infected animals and are able to survive for long periods in the environment. Infection of humans usually occurs by inhalation of these organisms from air that contains airborne barnyard dust contaminated by dried placental material, birth fluids, and waste products of infected animals. Other modes of transmission to humans, including tick bites, ingestion of unpasteurized milk or dairy products, and human to human transmission, are rare. Humans are often very susceptible to the disease, and very few organisms may be required to cause infection. In less than 5% of cases the affected people with acute Q fever infection develop a chronic Q fever. Treatment of the acute form is made with antibiotics. The chronic form's treatment depends on the symptoms. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Q fever	c0034362	3,910	gard	https://rarediseases.info.nih.gov/diseases/7515/q-fever	2021-01-18T17:58:01	{"mesh": ["D011778"], "orphanet": ["781"], "synonyms": ["Q fever pneumonia", "Coxiella Burnetii fever", "Query fever"]}
A rare, lethal type of achondrogenesis characterized by severe micromelia with very short fingers and toes, a flat face, a short neck, thickened soft tissue around the neck, hypoplasia of the thorax, protuberant abdomen, a hydropic fetal appearance and distinctive histological features of the cartilage. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Achondrogenesis type 1B	c0265274	3,911	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93298	2021-01-23T18:55:24	{"gard": ["460"], "mesh": ["C536016"], "omim": ["600972"], "umls": ["C0265274"], "icd-10": ["Q77.0"], "synonyms": ["Achondrogenesis, Parenti-Fraccaro type"]}
Primary microcephaly-mild intellectual disability-young-onset diabetes syndrome is a rare, genetic, syndromic intellectual disability disorder characterized by congenital, persistent microcephaly, low birth weight, short stature, childhood-onset seizures, global development delay, mild intellectual disability, and adolescent or young adult-onset diabetes mellitus. Gait ataxia, skeletal abnormalities, dorsocervical fat pad, and infantile cirrhosis may also be associated. Brain morphology is typically normal, although delayed myelination and hypoplastic brainstem have been reported. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Primary microcephaly-mild intellectual disability-young-onset diabetes syndrome	c4014997	3,912	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=391408	2021-01-23T16:56:54	{"omim": ["616033", "616817"], "icd-10": ["Q87.8"]}
For a discussion of the genetic heterogeneity in serum adiponectin levels, see ADIPQTL1 (612556). Mapping Adiponectin (ADIPOQ; 605441) is an exclusively adipocyte-derived protein expressed inversely to total fat and is thought to play a role in mediating the obesity-related risk for coronary artery disease and type 2 diabetes mellitus (125853). Comuzzie et al. (2001) assayed serum levels of adiponectin in 1,100 adults of predominantly northern European ancestry distributed across 170 families. Quantitative genetic analysis of adiponectin levels detected an additive genetic heritability of 46%. The maximum lod score detected in a genomewide scan for adiponectin levels was 4.06 (P = 7.7 x 10-6), 35 cM from pter near D5S817 on chromosome 5. The second largest lod score (lod = 3.2; P = 6.2 x 10-5) was detected on chromosome 14, 29 cM from pter (ADIPQTL3; 606771). The detection of a significant linkage with a quantitative trait locus on chromosome 5 provides strong evidence for a replication of a previously reported quantitative trait locus for obesity-related phenotypes. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	ADIPONECTIN, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS 2	c1847530	3,913	omim	https://www.omim.org/entry/606770	2019-09-22T16:10:02	{"omim": ["606770"], "synonyms": ["Alternative titles", "CIRCULATING ADIPONECTIN QUANTITATIVE TRAIT LOCUS ON CHROMOSOME 5"]}
A rare urogenital tract malformation characterized by the complete absence of the scrotal rugae in the perineum between the penis and anus, with bilateral testes being present in a cryptorchid or ectopic position. Hemiscrotal agenesis refers to the unilateral absence of scrotal skin with an intact midline raphe and ipsilateral cryptorchidism. Both malformations may be isolated findings, or occur in association with other anomalies. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Congenital agenesis of the scrotum	None	3,914	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=495879	2021-01-23T17:12:10	{"synonyms": ["Congenital absence of the scrotum", "Congenital scrotal absence", "Congenital scrotal agenesis"]}
Severe lateral tibial bowing with short stature is a rare, genetic, primary bent bone dysplasia characterized by significant, uni-/bilateral, lateral tibial bowing localized to the distal two-thirds of the tibia, with respective cortical thickening and thinning of the inner and outer tibial curve, loss of normal trabecular bone, bilateral abnormalities of the tibial epiphyses and growth plates, as well as foot abnormalities, including abnormally high arches. Affected individuals have short stature with absence of other skeletal abnormalities. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis *[DDD]: degenerative disc disease	Severe lateral tibial bowing with short stature	c4707850	3,915	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=324307	2021-01-23T17:09:52	{"icd-10": ["Q68.4"]}
Blood clot (thrombus) that forms within a vein Venous thrombosis A deep vein thrombosis in the right leg. There is striking redness and swelling. SpecialtyHematology, pulmonology, cardiology Frequency1-2 per 1,000 per year[1] Venous thrombosis is thrombosis in a vein, caused by a thrombus (blood clot). The most common form of venous thrombosis is a deep vein thrombosis (DVT), when a blood clot forms in the deep veins of the leg. If the thrombus breaks off (it embolizes) and flows towards the lungs, it can become a pulmonary embolism (PE), a blood clot in the lungs. This combination is called venous thromboembolism. Various other forms of venous thrombosis also exist; some of these can also lead to pulmonary embolism. The initial treatment for venous thromboembolism is typically with either low molecular weight heparin (LMWH) or unfractionated heparin, or increasingly with directly acting oral anticoagulants (DOAC). Those initially treated with heparins can be switched to other anticoagulants (warfarin, DOACs), although pregnant women and some people with cancer receive ongoing heparin treatment. Superficial venous thrombosis only requires anticoagulation in specific situations, and may be treated with anti-inflammatory pain relief only. ## Contents * 1 Classification * 1.1 Common forms * 1.2 Rare forms * 1.3 Parodoxical embolism * 2 Causes * 2.1 Risk factors * 2.1.1 Acquired * 2.1.2 Inherited * 2.1.3 Mixed * 3 Pathophysiology * 4 Prevention * 5 Treatment * 5.1 Anticoagulation * 5.2 Thrombolysis * 5.3 Inferior vena cava filters * 5.4 Superficial venous thrombosis * 6 Prognosis * 7 See also * 8 References * 9 External links ## Classification[edit] ### Common forms[edit] Superficial venous thromboses cause discomfort but generally not serious consequences, as do the deep vein thromboses (DVTs) that form in the deep veins of the legs or in the pelvic veins. Nevertheless, they can progress to the deep veins through the perforator veins or, they can be responsible for a lung embolism mainly if the head of the clot is poorly attached to the vein wall and is situated near the sapheno-femoral junction.[citation needed] When a blood clot breaks loose and travels in the blood, this is called a venous thromboembolism (VTE). The abbreviation DVT/PE refers to a VTE where a deep vein thrombosis (DVT) has moved to the lungs (PE or pulmonary embolism).[2] Since the veins return blood to the heart, if a piece of a blood clot formed in a vein breaks off it can be transported to the right side of the heart, and from there into the lungs. A piece of thrombus that is transported in this way is an embolus: the process of forming a thrombus that becomes embolic is called a thromboembolism. An embolism that lodges in the lungs is a pulmonary embolism (PE). A pulmonary embolism is a very serious condition that can be fatal depending on the dimensions of the embolus.[citation needed] ### Rare forms[edit] While venous thrombosis of the legs is the most common form, venous thrombosis may occur in other veins. These may have particular specific risk factors:[3] * Cerebral venous sinus thrombosis, cavernous sinus thrombosis and jugular vein thrombosis: thrombosis of the veins of the brain and head * Central retinal vein occlusion and branch retinal vein occlusion: despite the name these conditions have much more in common with arterial thrombosis and are not treated with anticoagulants * Paget–Schroetter disease: thrombosis of the veins of the arms (axillary and subclavian veins) * Budd-Chiari syndrome (thrombosis of the hepatic vein) * Thrombosis of the hepatic portal system: * Thrombosis of the superior mesenteric vein, which may cause mesenteric ischemia (insufficient blood flow to the intestine) * Portal vein thrombosis * Thrombosis of the splenic vein * Renal vein thrombosis (thrombosis of the veins of the kidneys) ### Parodoxical embolism[edit] Systemic embolism of venous origin can occur in patients with an atrial or ventricular septal defect, or an arteriovenous connection in the lung, through which an embolus may pass into the arterial system. Such an event is termed a paradoxical embolism. When this affects the blood vessels of the brain it can cause stroke.[4] ## Causes[edit] Venous thrombi are caused mainly by a combination of venous stasis and hypercoagulability—but to a lesser extent endothelial damage and activation.[5] The three factors of stasis, hypercoaguability, and alterations in the blood vessel wall represent Virchow's triad, and changes to the vessel wall are the least understood.[6] Various risk factors increase the likelihood of any one individual developing a thrombosis. ### Risk factors[edit] #### Acquired[edit] * Older age[6] * Major surgery, orthopedic surgery,[7] neurosurgery[8] * Cancers, most particularly pancreatic, but not cancers of the lip, oral cavity, and pharynx[9] * Immobilization, as in orthopedic casts[7] the sitting position, and travel, particularly by air[5] * Pregnancy and the postpartum period[5][10] * Antiphospholipid syndrome[7] (such as lupus anticoagulant)[5][6] * Trauma[5] and minor leg injury[11] * Previous VTE[12] * Oral contraceptives[7] * Hormonal replacement therapy,[7] esp. oral * Central venous catheters[7][13] * Inflammatory diseases[14]/some autoimmune diseases[15] * Nephrotic syndrome[16] * Obesity[7] * Infection[16] * HIV[16] * Myeloproliferative neoplasms including essential thrombocytosis and polycythemia vera[7] * Chemotherapy[6][17] * Heart failure[18] #### Inherited[edit] * Antithrombin deficiency[5] * Protein C deficiency[5] * Protein S deficiency (type I)[16] * Factor V Leiden[5] * Prothrombin G20210A[5] * Dysfibrinogenemia[7] * Non O-blood type[19] #### Mixed[edit] * Low free protein S[16] * Activated protein C resistance[16] * High factor VIII levels[20] * Hyperhomocysteinemia[5] * High fibrinogen levels[5] * High factor IX levels[5] * High factor XI levels[5] The overall absolute risk of venous thrombosis per 100,000 woman years in current use of combined oral contraceptives is approximately 60, compared to 30 in non-users.[21] The risk of thromboembolism varies with different types of birth control pills; Compared with combined oral contraceptives containing levonorgestrel (LNG), and with the same dose of estrogen and duration of use, the rate ratio of deep vein thrombosis for combined oral contraceptives with norethisterone is 0.98, with norgestimate 1.19, with desogestrel (DSG) 1.82, with gestodene 1.86, with drospirenone (DRSP) 1.64, and with cyproterone acetate 1.88.[21] Venous thromboembolism occurs in 100–200 per 100,000 pregnant women every year.[21] Regarding family history, age has substantial effect modification. For individuals with two or more affected siblings, the highest incidence rates is found among those ≥70 years of age (390 per 100,000 in male and 370 per 100,000 in female individuals), whereas the highest incidence ratios compared to those without affected siblings occurred at much younger ages (ratio of 4.3 among male individuals 20 to 29 years of age and 5.5 among female individuals 10 to 19 years of age).[22] * v * t * e Risk of venous thromboembolism (VTE) with hormone therapy and birth control (QResearch/CPRD) Type Route Medications Odds ratio (95% CI) Menopausal hormone therapy Oral Estradiol alone ≤1 mg/day >1 mg/day 1.27 (1.16–1.39)* 1.22 (1.09–1.37)* 1.35 (1.18–1.55)* Conjugated estrogens alone ≤0.625 mg/day >0.625 mg/day 1.49 (1.39–1.60)* 1.40 (1.28–1.53)* 1.71 (1.51–1.93)* Estradiol/medroxyprogesterone acetate 1.44 (1.09–1.89)* Estradiol/dydrogesterone ≤1 mg/day E2 >1 mg/day E2 1.18 (0.98–1.42) 1.12 (0.90–1.40) 1.34 (0.94–1.90) Estradiol/norethisterone ≤1 mg/day E2 >1 mg/day E2 1.68 (1.57–1.80)* 1.38 (1.23–1.56)* 1.84 (1.69–2.00)* Estradiol/norgestrel or estradiol/drospirenone 1.42 (1.00–2.03) Conjugated estrogens/medroxyprogesterone acetate 2.10 (1.92–2.31)* Conjugated estrogens/norgestrel ≤0.625 mg/day CEEs >0.625 mg/day CEEs 1.73 (1.57–1.91)* 1.53 (1.36–1.72)* 2.38 (1.99–2.85)* Tibolone alone 1.02 (0.90–1.15) Raloxifene alone 1.49 (1.24–1.79)* Transdermal Estradiol alone ≤50 μg/day >50 μg/day 0.96 (0.88–1.04) 0.94 (0.85–1.03) 1.05 (0.88–1.24) Estradiol/progestogen 0.88 (0.73–1.01) Vaginal Estradiol alone 0.84 (0.73–0.97) Conjugated estrogens alone 1.04 (0.76–1.43) Combined birth control Oral Ethinylestradiol/norethisterone 2.56 (2.15–3.06)* Ethinylestradiol/levonorgestrel 2.38 (2.18–2.59)* Ethinylestradiol/norgestimate 2.53 (2.17–2.96)* Ethinylestradiol/desogestrel 4.28 (3.66–5.01)* Ethinylestradiol/gestodene 3.64 (3.00–4.43)* Ethinylestradiol/drospirenone 4.12 (3.43–4.96)* Ethinylestradiol/cyproterone acetate 4.27 (3.57–5.11)* Notes: (1) Nested case–control studies (2015, 2019) based on data from the QResearch and Clinical Practice Research Datalink (CPRD) databases. (2) Bioidentical progesterone was not included, but is known to be associated with no additional risk relative to estrogen alone. Footnotes: * = Statistically significant (p < 0.01). Sources: See template. * v * t * e Absolute and relative incidence of venous thromboembolism (VTE) during pregnancy and the postpartum period Absolute incidence of first VTE per 10,000 person–years during pregnancy and the postpartum period Swedish data A Swedish data B English data Danish data Time period N Rate (95% CI) N Rate (95% CI) N Rate (95% CI) N Rate (95% CI) Outside pregnancy 1105 4.2 (4.0–4.4) 1015 3.8 (?) 1480 3.2 (3.0–3.3) 2895 3.6 (3.4–3.7) Antepartum 995 20.5 (19.2–21.8) 690 14.2 (13.2–15.3) 156 9.9 (8.5–11.6) 491 10.7 (9.7–11.6) Trimester 1 207 13.6 (11.8–15.5) 172 11.3 (9.7–13.1) 23 4.6 (3.1–7.0) 61 4.1 (3.2–5.2) Trimester 2 275 17.4 (15.4–19.6) 178 11.2 (9.7–13.0) 30 5.8 (4.1–8.3) 75 5.7 (4.6–7.2) Trimester 3 513 29.2 (26.8–31.9) 340 19.4 (17.4–21.6) 103 18.2 (15.0–22.1) 355 19.7 (17.7–21.9) Around delivery 115 154.6 (128.8–185.6) 79 106.1 (85.1–132.3) 34 142.8 (102.0–199.8) – Postpartum 649 42.3 (39.2–45.7) 509 33.1 (30.4–36.1) 135 27.4 (23.1–32.4) 218 17.5 (15.3–20.0) Early postpartum 584 75.4 (69.6–81.8) 460 59.3 (54.1–65.0) 177 46.8 (39.1–56.1) 199 30.4 (26.4–35.0) Late postpartum 65 8.5 (7.0–10.9) 49 6.4 (4.9–8.5) 18 7.3 (4.6–11.6) 319 3.2 (1.9–5.0) Incidence rate ratios (IRRs) of first VTE during pregnancy and the postpartum period Swedish data A Swedish data B English data Danish data Time period IRR* (95% CI) IRR* (95% CI) IRR (95% CI)† IRR (95% CI)† Outside pregnancy Reference (i.e., 1.00) Antepartum 5.08 (4.66–5.54) 3.80 (3.44–4.19) 3.10 (2.63–3.66) 2.95 (2.68–3.25) Trimester 1 3.42 (2.95–3.98) 3.04 (2.58–3.56) 1.46 (0.96–2.20) 1.12 (0.86–1.45) Trimester 2 4.31 (3.78–4.93) 3.01 (2.56–3.53) 1.82 (1.27–2.62) 1.58 (1.24–1.99) Trimester 3 7.14 (6.43–7.94) 5.12 (4.53–5.80) 5.69 (4.66–6.95) 5.48 (4.89–6.12) Around delivery 37.5 (30.9–44.45) 27.97 (22.24–35.17) 44.5 (31.68–62.54) – Postpartum 10.21 (9.27–11.25) 8.72 (7.83–9.70) 8.54 (7.16–10.19) 4.85 (4.21–5.57) Early postpartum 19.27 (16.53–20.21) 15.62 (14.00–17.45) 14.61 (12.10–17.67) 8.44 (7.27–9.75) Late postpartum 2.06 (1.60–2.64) 1.69 (1.26–2.25) 2.29 (1.44–3.65) 0.89 (0.53–1.39) Notes: Swedish data A = Using any code for VTE regardless of confirmation. Swedish data B = Using only algorithm-confirmed VTE. Early postpartum = First 6 weeks after delivery. Late postpartum = More than 6 weeks after delivery. * = Adjusted for age and calendar year. † = Unadjusted ratio calculated based on the data provided. Source: [23] ## Pathophysiology[edit] In contrast to the understanding for how arterial thromboses occur, as with heart attacks, venous thrombosis formation is not well understood.[24] With arterial thrombosis, blood vessel wall damage is required for thrombosis formation, as it initiates coagulation,[24] but the majority of venous thrombi form without any injured epithelium.[5] Red blood cells and fibrin are the main components of venous thrombi,[5] and the thrombi appear to attach to the blood vessel wall endothelium, normally a non-thrombogenic surface, with fibrin.[24] Platelets in venous thrombi attach to downstream fibrin, while in arterial thrombi, they compose the core.[24] As a whole, platelets constitute less of venous thrombi when compared to arterial ones.[5] The process is thought to be initiated by tissue factor-affected thrombin production, which leads to fibrin deposition.[6] The valves of veins are a recognized site of VT initiation. Due to the blood flow pattern, the base of the valve sinus is particularly deprived of oxygen (hypoxic). Stasis excacerbates hypoxia, and this state is linked to the activation of white blood cells (leukocytes) and the endothelium. Specifically, the two pathways of hypoxia-inducible factor-1 (HIF-1) and early growth response 1 (EGR-1) are activated by hypoxia, and they contribute to monocyte and endothelial activation. Hypoxia also causes reactive oxygen species (ROS) production that can activate HIF-1, EGR-1, and nuclear factor-κB (NF-κB), which regulates HIF-1 transcription.[6] HIF-1 and EGR-1 pathways lead to monocyte association with endothelial proteins, such as P-selectin, prompting monocytes to release tissue factor-filled microvesicles, which presumably initiate fibrin deposition (via thrombin) after binding the endothelial surface.[6] ## Prevention[edit] Main article: Thrombosis prophylaxis Evidence supports the use of heparin in people following surgery who have a high risk of thrombosis to reduce the risk of DVTs; however, the effect on PEs or overall mortality is not known.[25] In hospitalized non-surgical patients, mortality does not appear to change.[26][27][28] It does not appear, however, to decrease the rate of symptomatic DVTs.[26] Using both heparin and compression stockings appears better than either one alone in reducing the rate of DVT.[29] In hospitalized people who have had a stroke and not had surgery, mechanical measures (compression stockings) resulted in skin damage and no clinical improvement.[26] Data on the effectiveness of compression stockings among hospitalized non-surgical patients without stroke is scarce.[26] The American College of Physicians (ACP) gave three strong recommendations with moderate quality evidence on VTE prevention in non-surgical patients: that hospitalized patients be assessed for their risk of thromboembolism and bleeding before prophylaxis (prevention); that heparin or a related drug is used if potential benefits are thought to outweigh potential harms; and that graduated compression stockings not be used.[30] As an ACP policy implication, the guideline stated a lack of support for any performance measures that incentivize physicians to apply universal prophylaxis without regard to the risks.[30] Goldhaber recommends that people should be assessed at their hospital discharge for persistent high-risk of venous thrombosis and that people who adopt a heart-healthy lifestyle might lower their risk of venous thrombosis.[31] People who have cancer have a higher risk of VTE and may respond differently to anticoagulant preventative treatments and prevention measures.[32] For people undergoing chemotherapy for cancer who are able to walk (ambulatory), low molecular weight heparins treatment (LMWH) decreases the risk of VTE.[33] Due to potential concerns of bleeding its routine use is not recommended.[33] For people who are having surgery for cancer, it is recommended that they receive anticoagulation therapy (preferably LMWH) in order to prevent a VTE.[34] LMWH is recommended for at least 7–10 days following cancer surgery, and for one month following surgery for people who have a high risk of VTEs.[35][34] In adults who have had their lower leg casted, braced, or otherwise immobilized for more than a week, LMWH may decrease the risk and severity of deep vein thrombosis, but does not have any effect on the incidence of pulmonary embolism .[36] LMWH is recommended for adults not in hospital with an above-knee cast and a below-knee cast, and is safe for this indication.[37][needs update] Following the completion of warfarin in those with prior VTE, the use of long-term aspirin has been show to be beneficial.[38] ## Treatment[edit] American evidence-based clinical guidelines were published in 2016 for the treatment of VTE.[39] In the UK, guidelines by the National Institute for Health and Care Excellence (NICE) were published in 2012, updated in 2020.[40] These guidelines do not cover rare forms of thrombosis, for which an individualized approach is often needed.[3] Central and branch retinal vein occlusion does not benefit from anticoagulation in the way that other venous thromboses do.[3] ### Anticoagulation[edit] If diagnostic testing cannot be performed swiftly, many are commenced on empirical treatment.[40] Traditionally this was heparin, but several of the DOACs are licensed for treatment without initial heparin use.[39] If heparin is used for initial treatment of VTE, fixed doses with low molecular weight heparin may be more effective than adjusted doses of unfractionated heparin (UFH) in reducing blood clots.[41] No differences in mortality, prevention of major bleeding, or preventing VTEs from recurring were observed between LMWH and UFH.[42] No differences have been detected in the route of administration of UFH (subcutaneous or intravenous).[41] LMWH is usually administered by a subcutaneous injection, and a person's blood clotting factors do not have to be monitored as closely as with UFH.[41] Once the diagnosis is confirmed, a decision needs to be made about the nature of the ongoing treatment and its duration. USA recommendations for those without cancer include anticoagulation (medication that prevents further blood clots from forming) with the DOACs dabigatran, rivaroxaban, apixaban, or edoxaban rather than warfarin or low molecular weight heparin (LMWH).[39] For those with cancer, LMWH is recommended,[39] although DOACs appear safe in the majority of situations.[40] For long-term treatment in people with cancer, LMWH is probably more effective at reducing VTEs when compared to vitamin K antagonists.[32] People with cancer have a higher risk of experiencing reoccurring VTE episodes ("recurrent VTE"), even while taking preventative anticoagulation medication. These people should be given therapeutic doses of LMWH medication, either by switching from another anticoagulant or by taking a higher dose of LMWH.[43] In pregnancy, warfarin and DOACs are not considered suitable and LMWH is recommended.[39] For those with a small pulmonary embolism and few risk factors, no anticoagulation is needed.[39] Anticoagulation is, however, recommended in those who do have risk factors.[39] ### Thrombolysis[edit] Thrombolysis is the administration of medication (a recombinant enzyme) that activates plasmin, the body's main enzyme that breaks down blood clots. This carries a risk of bleeding and is therefore reserved for those who have a form of thrombosis that may cause major complications. In pulmonary embolism, this applies in situations where heart function is compromised due to lack of blood flow through the lungs ("massive" or "high risk" pulmonary embolism), leading to low blood pressure.[39] Deep vein thrombosis may require thrombolysis if there is a significant risk of post-thrombotic syndrome.[39] Thrombolysis may be administered by intravenous catheter directly into the clot ("catheter-directed thrombolysis"); this requires a lower dose of the medication and may carry a lower bleeding risk but evidence for its benefit is limited.[39] ### Inferior vena cava filters[edit] Inferior vena cava filters (IVCFs) are not recommended in those who are on anticoagulants.[39] IVCFs may be used in clinical situations where a person has a high risk of experiencing a pulmonary embolism, but cannot be on anticoagulants due to a high risk of bleeding, or they have active bleeding.[43][44] Retrievable IVCFs are recommended if IVCFs must be used, and a plan should be created to remove the filter when it is no longer needed.[43] ### Superficial venous thrombosis[edit] While topical treatments for superficial venous thrombosis are widely used, the evidence is strongest for the heparin-like drug fondaparinux (a factor Xa inhibitor), which reduces extension and recurrence of superficial venous thrombosis as well as progression to symptomatic embolism.[45] ## Prognosis[edit] After an episode of unprovoked VTE, the risk of further episodes after completing treatment remains elevated, although this risk diminishes over time. Over ten years, 41% of men and 29% of women can expect to experience a further episode. For each episode, the risk of death is 4%.[46] ## See also[edit] * Portal vein thrombosis * Arterial thrombosis ## References[edit] 1. ^ Ortel, TL; Neumann, I; Ageno, W; et al. (13 October 2020). "American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism". Blood Advances. 4 (19): 4693–4738. doi:10.1182/bloodadvances.2020001830. PMC 7556153. PMID 33007077. 2. ^ National Clinical Guideline Centre – Acute and Chronic Conditions (UK) (2010). "Venous Thromboembolism: Reducing the Risk of Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism) in Patients Admitted to Hospital". PMID 23346611. Cite journal requires `\|journal=` (help) 3. ^ a b c Shatzel, Joseph J.; O'Donnell, Matthew; Olson, Sven R.; Kearney, Matthew R.; Daughety, Molly M.; Hum, Justine; Nguyen, Khanh P.; DeLoughery, Thomas G. (January 2019). "Venous thrombosis in unusual sites: A practical review for the hematologist". European Journal of Haematology. 102 (1): 53–62. doi:10.1111/ejh.13177. ISSN 0902-4441. PMID 30267448. 4. ^ Windecker, Stephan; Stortecky, Stefan; Meier, Bernhard (July 2014). "Paradoxical Embolism". Journal of the American College of Cardiology. 64 (4): 403–415. doi:10.1016/j.jacc.2014.04.063. PMID 25060377. 5. ^ a b c d e f g h i j k l m n o p Martinelli I, Bucciarelli P, Mannucci PM (2010). "Thrombotic risk factors: basic pathophysiology". Crit Care Med. 38 (suppl 2): S3–9. doi:10.1097/CCM.0b013e3181c9cbd9. PMID 20083911. S2CID 34486553. 6. ^ a b c d e f g Bovill EG, van der Vliet A (2011). "Venous valvular stasis-associated hypoxia and thrombosis: what is the link?". Annu Rev Physiol. 73: 527–45. doi:10.1146/annurev-physiol-012110-142305. PMID 21034220. 7. ^ a b c d e f g h i Rosendaal FR, Reitsma PH (2009). "Genetics of venous thrombosis". J. Thromb. Haemost. 7 (suppl 1): 301–4. doi:10.1111/j.1538-7836.2009.03394.x. PMID 19630821. S2CID 27104496. 8. ^ Khan NR, Patel PG, Sharpe JP, Lee SL, Sorenson J (2018). "Chemical venous thromboembolism prophylaxis in neurosurgical patients: an updated systematic review and meta-analysis". Journal of Neurosurgery. 129 (4): 906–915. doi:10.3171/2017.2.JNS162040. PMID 29192859. S2CID 37464528. "Patients requiring cranial and spinal surgery present a unique situation of elevated risk for VTE but also high risk for disastrous outcomes should bleeding complications occur in eloquent areas of the brain or spinal cord." 9. ^ Stein PD, Beemath A, Meyers FA, et al. (2006). "Incidence of venous thromboembolism in patients hospitalized with cancer". Am J Med. 119 (1): 60–8. doi:10.1016/j.amjmed.2005.06.058. PMID 16431186. 10. ^ Jackson E, Curtis KM, Gaffield ME (2011). "Risk of venous thromboembolism during the postpartum period: a systematic review". Obstet Gynecol. 117 (3): 691–703. doi:10.1097/AOG.0b013e31820ce2db. PMID 21343773. S2CID 12561. 11. ^ Varga EA, Kujovich JL (2012). "Management of inherited thrombophilia: guide for genetics professionals". Clin Genet. 81 (1): 7–17. doi:10.1111/j.1399-0004.2011.01746.x. PMID 21707594. S2CID 9305488. 12. ^ Turpie AGG (March 2008). "Deep Venous Thrombosis". The Merck's Manuals Online Medical Library. Merck. 13. ^ Beyer-Westendorf J, Bauersachs R, Hach-Wunderle V, Zotz RB, Rott H. Sex hormones and venous thromboembolism - from contraception to hormone replacement therapy. Vasa. 2018 Jul 16:1-10.2018/07/17 14. ^ Reitsma PH, Versteeg HH, Middeldorp S (2012). "Mechanistic view of risk factors for venous thromboembolism". Arterioscler Thromb Vasc Biol. 32 (3): 563–8. doi:10.1161/ATVBAHA.111.242818. PMID 22345594. S2CID 2624599. 15. ^ Zöller B, Li X, Sundquist J, et al. (2012). "Risk of pulmonary embolism in patients with autoimmune disorders: a nationwide follow-up study from Sweden". Lancet. 379 (9812): 244–9. doi:10.1016/S0140-6736(11)61306-8. PMID 22119579. S2CID 11612703. 16. ^ a b c d e f Lijfering WM, Rosendaal FR, Cannegieter SC (2010). "Risk factors for venous thrombosis – current understanding from an epidemiological point of view". Br J Haematol. 149 (6): 824–33. doi:10.1111/j.1365-2141.2010.08206.x. PMID 20456358. S2CID 41684138. 17. ^ Mandalà, M; Falanga, A; Roila, F; ESMO Guidelines Working, Group. (September 2011). "Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines". Annals of Oncology. 22 Suppl 6: vi85–92. doi:10.1093/annonc/mdr392. PMID 21908511. 18. ^ Tang L, Wu YY, Lip GY, Yin P, Hu Y (January 2016). "Heart failure and risk of venous thromboembolism: a systematic review and meta-analysis". Lancet Haematol. 3 (1): e30–44. doi:10.1016/S2352-3026(15)00228-8. PMID 26765646. 19. ^ Dentali F, Sironi AP, Ageno W, et al. (2012). "Non-O Blood Type Is the Commonest Genetic Risk Factor for VTE: Results from a Meta-Analysis of the Literature". Semin. Thromb. Hemost. 38 (5): 535–48. doi:10.1055/s-0032-1315758. PMID 22740183. 20. ^ Jenkins PV, Rawley O, Smith OP, et al. (2012). "Elevated factor VIII levels and risk of venous thrombosis". Br J Haematol. 157 (6): 653–63. doi:10.1111/j.1365-2141.2012.09134.x. PMID 22530883. S2CID 24467063. 21. ^ a b c Eichinger, S.; Evers, J. L. H.; Glasier, A.; La Vecchia, C.; Martinelli, I.; Skouby, S.; Somigliana, E.; Baird, D. T.; Benagiano, G.; Crosignani, P. G.; Gianaroli, L.; Negri, E.; Volpe, A.; Glasier, A.; Crosignani, P. G. (2013). "Venous thromboembolism in women: A specific reproductive health risk". Human Reproduction Update. 19 (5): 471–482. doi:10.1093/humupd/dmt028. PMID 23825156. 22. ^ Eikelboom, J. W.; Weitz, J. I. (2011). "Importance of family history as a risk factor for venous thromboembolism". Circulation. 124 (9): 996–7. doi:10.1161/CIRCULATIONAHA.111.048868. PMID 21875920. 23. ^ Abdul Sultan A, West J, Stephansson O, Grainge MJ, Tata LJ, Fleming KM, Humes D, Ludvigsson JF (November 2015). "Defining venous thromboembolism and measuring its incidence using Swedish health registries: a nationwide pregnancy cohort study". BMJ Open. 5 (11): e008864. doi:10.1136/bmjopen-2015-008864. PMC 4654387. PMID 26560059. 24. ^ a b c d López JA, Chen J (2009). "Pathophysiology of venous thrombosis". Thromb Res. 123 (Suppl 4): S30–4. doi:10.1016/S0049-3848(09)70140-9. PMID 19303501. 25. ^ Roderick, P; Ferris, G; Wilson, K; Halls, H; Jackson, D; Collins, R; Baigent, C (December 2005). "Towards evidence-based guidelines for the prevention of venous thromboembolism: systematic reviews of mechanical methods, oral anticoagulation, dextran and regional anaesthesia as thromboprophylaxis". Health Technology Assessment (Winchester, England). 9 (49): iii–iv, ix–x, 1–78. doi:10.3310/hta9490. PMID 16336844. 26. ^ a b c d Lederle, FA; Zylla, D; Macdonald, R; Wilt, TJ (2011-11-01). "Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: a background review for an american college of physicians clinical practice guideline". Annals of Internal Medicine. 155 (9): 602–15. doi:10.7326/0003-4819-155-9-201111010-00008. PMID 22041949. S2CID 207536371. 27. ^ Alikhan, R; Bedenis, R; Cohen, AT (7 May 2014). "Heparin for the prevention of venous thromboembolism in acutely ill medical patients (excluding stroke and myocardial infarction)". The Cochrane Database of Systematic Reviews (5): CD003747. doi:10.1002/14651858.CD003747.pub4. PMC 6491079. PMID 24804622. 28. ^ "[120] Routine VTE prophylaxis: Is there a net health benefit?". Therapeutics Initiative. 16 July 2019. 29. ^ Zareba, P; Wu, C; Agzarian, J; Rodriguez, D; Kearon, C (Aug 2014). "Meta-analysis of randomized trials comparing combined compression and anticoagulation with either modality alone for prevention of venous thromboembolism after surgery". The British Journal of Surgery. 101 (9): 1053–62. doi:10.1002/bjs.9527. PMID 24916118. S2CID 37373926. 30. ^ a b Qaseem A, Chou R, Humphrey LL, Starkey M, Shekelle P (November 2011). "Venous thromboembolism prophylaxis in hospitalized patients: a clinical practice guideline from the American College of Physicians". Ann. Intern. Med. 155 (9): 625–32. CiteSeerX 10.1.1.689.591. doi:10.7326/0003-4819-155-9-201111010-00011. PMID 22041951. S2CID 7129943. 31. ^ Goldhaber, Samuel Z. (2010). "Risk Factors for Venous Thromboembolism". Journal of the American College of Cardiology. 56 (1): 1–7. doi:10.1016/j.jacc.2010.01.057. PMID 20620709. 32. ^ a b Kahale, Lara A.; Hakoum, Maram B.; Tsolakian, Ibrahim G.; Matar, Charbel F.; Terrenato, Irene; Sperati, Francesca; Barba, Maddalena; Yosuico, Victor Ed; Schünemann, Holger (2018). "Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer". The Cochrane Database of Systematic Reviews. 6: CD006650. doi:10.1002/14651858.CD006650.pub5. ISSN 1469-493X. PMC 6389342. PMID 29920657. 33. ^ a b Di Nisio, Marcello; Porreca, Ettore; Candeloro, Matteo; De Tursi, Michele; Russi, Ilaria; Rutjes, Anne Ws (2016-12-01). "Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy" (PDF). The Cochrane Database of Systematic Reviews. 12: CD008500. doi:10.1002/14651858.CD008500.pub4. ISSN 1469-493X. PMC 6463937. PMID 27906452. 34. ^ a b Mandalà, M.; Falanga, A.; Roila, F.; ESMO Guidelines Working Group (2011-09-01). "Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines". Annals of Oncology. 22 Suppl 6: vi85–92. doi:10.1093/annonc/mdr392. ISSN 1569-8041. PMID 21908511. 35. ^ Christensen, Thomas D.; Vad, Henrik; Pedersen, Søren; Hvas, Anne-Mette; Wotton, Robin; Naidu, Babu; Larsen, Torben B. (2014-02-01). "Venous thromboembolism in patients undergoing operations for lung cancer: a systematic review". The Annals of Thoracic Surgery. 97 (2): 394–400. doi:10.1016/j.athoracsur.2013.10.074. ISSN 1552-6259. PMID 24365217. 36. ^ Zee, AA; van Lieshout, K; van der Heide, M; Janssen, L; Janzing, HM (Apr 25, 2017). "Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-leg immobilization". The Cochrane Database of Systematic Reviews. 8: CD006681. doi:10.1002/14651858.CD006681.pub4. PMC 6483324. PMID 28780771. 37. ^ Testroote, M; Stigter, WA; Janssen, L; Janzing, HM (Apr 25, 2014). "Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-leg immobilization". The Cochrane Database of Systematic Reviews. 4 (4): CD006681. doi:10.1002/14651858.CD006681.pub3. PMID 24771319. 38. ^ Simes, J; Becattini, C; Agnelli, G; Eikelboom, JW; Kirby, AC; Mister, R; Prandoni, P; Brighton, TA; INSPIRE Study Investigators (International Collaboration of Aspirin Trials for Recurrent Venous, Thromboembolism) (23 September 2014). "Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration". Circulation. 130 (13): 1062–71. doi:10.1161/circulationaha.114.008828. PMID 25156992. 39. ^ a b c d e f g h i j k Kearon, C; Akl, EA; Ornelas, J; Blaivas, A; Jimenez, D; Bounameaux, H; Huisman, M; King, CS; Morris, TA; Sood, N; Stevens, SM; Vintch, JR; Wells, P; Woller, SC; Moores, L (February 2016). "Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report". Chest. 149 (2): 315–52. doi:10.1016/j.chest.2015.11.026. PMID 26867832. 40. ^ a b c "Venous thromboembolic diseases: diagnosis, management and thrombophilia testing". www.nice.org.uk. National Institute for Health and Care Excellence. 2020. Retrieved 2020-08-31. 41. ^ a b c Robertson, Lindsay; Jones, Lauren E. (2017-02-09). "Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism". The Cochrane Database of Systematic Reviews. 2: CD001100. doi:10.1002/14651858.CD001100.pub4. ISSN 1469-493X. PMC 6464611. PMID 28182249. 42. ^ Robertson L, Strachan J (February 2017). "Subcutaneous unfractionated heparin for the initial treatment of venous thromboembolism". Cochrane Database Syst Rev. 2: CD006771. doi:10.1002/14651858.CD006771.pub3. PMC 6464347. PMID 28195640. 43. ^ a b c Khorana, Alok A.; Carrier, Marc; Garcia, David A.; Lee, Agnes Y. Y. (2016-01-01). "Guidance for the prevention and treatment of cancer-associated venous thromboembolism". Journal of Thrombosis and Thrombolysis. 41 (1): 81–91. doi:10.1007/s11239-015-1313-4. ISSN 1573-742X. PMC 4715852. PMID 26780740. 44. ^ Rajasekhar, Anita (2015-04-01). "Inferior vena cava filters: current best practices". Journal of Thrombosis and Thrombolysis. 39 (3): 315–327. doi:10.1007/s11239-015-1187-5. ISSN 1573-742X. PMID 25680894. S2CID 5868257. 45. ^ Di Nisio, Marcello; Wichers, Iris M; Middeldorp, Saskia (2018-02-25). Cochrane Vascular Group (ed.). "Treatment for superficial thrombophlebitis of the leg". Cochrane Database of Systematic Reviews. 2: CD004982. doi:10.1002/14651858.CD004982.pub6. PMC 6491080. PMID 29478266. 46. ^ Khan, Faizan; Rahman, Alvi; Carrier, Marc; Kearon, Clive; Weitz, Jeffrey I; Schulman, Sam; Couturaud, Francis; Eichinger, Sabine; Kyrle, Paul A (2019-07-24). "Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis". BMJ. 366: l4363. doi:10.1136/bmj.l4363. PMC 6651066. PMID 31340984. ## External links[edit] Classification D * ICD-10: I80-I82 * ICD-9-CM: 453 * MeSH: D020246 * Postgraduate Medicine Journal: A Clinical Review of Venous Thromboembolism * v * t * e Cardiovascular disease (vessels) Arteries, arterioles and capillaries Inflammation * Arteritis * Aortitis * Buerger's disease Peripheral artery disease Arteriosclerosis * Atherosclerosis * Foam cell * Fatty streak * Atheroma * Intermittent claudication * Critical limb ischemia * Monckeberg's arteriosclerosis * Arteriolosclerosis * Hyaline * Hyperplastic * Cholesterol * LDL * Oxycholesterol * Trans fat Stenosis * Carotid artery stenosis * Renal artery stenosis Other * Aortoiliac occlusive disease * Degos disease * Erythromelalgia * Fibromuscular dysplasia * Raynaud's phenomenon Aneurysm / dissection / pseudoaneurysm * torso: Aortic aneurysm * Abdominal aortic aneurysm * Thoracic aortic aneurysm * Aneurysm of sinus of Valsalva * Aortic dissection * Aortic rupture * Coronary artery aneurysm * head / neck * Intracranial aneurysm * Intracranial berry aneurysm * Carotid artery dissection * Vertebral artery dissection * Familial aortic dissection Vascular malformation * Arteriovenous fistula * Arteriovenous malformation * Telangiectasia * Hereditary hemorrhagic telangiectasia Vascular nevus * Cherry hemangioma * Halo nevus * Spider angioma Veins Inflammation * Phlebitis Venous thrombosis / Thrombophlebitis * primarily lower limb * Deep vein thrombosis * abdomen * Hepatic veno-occlusive disease * Budd–Chiari syndrome * May–Thurner syndrome * Portal vein thrombosis * Renal vein thrombosis * upper limb / torso * Mondor's disease * Paget–Schroetter disease * head * Cerebral venous sinus thrombosis * Post-thrombotic syndrome Varicose veins * Gastric varices * Portacaval anastomosis * Caput medusae * Esophageal varices * Hemorrhoid * Varicocele Other * Chronic venous insufficiency * Chronic cerebrospinal venous insufficiency * Superior vena cava syndrome * Inferior vena cava syndrome * Venous ulcer Arteries or veins * Angiopathy * Macroangiopathy * Microangiopathy * Embolism * Pulmonary embolism * Cholesterol embolism * Paradoxical embolism * Thrombosis * Vasculitis Blood pressure Hypertension * Hypertensive heart disease * Hypertensive emergency * Hypertensive nephropathy * Essential hypertension * Secondary hypertension * Renovascular hypertension * Benign hypertension * Pulmonary hypertension * Systolic hypertension * White coat hypertension Hypotension * Orthostatic hypotension [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Venous thrombosis	c0149871	3,916	wikipedia	https://en.wikipedia.org/wiki/Venous_thrombosis	2021-01-18T18:49:19	{"mesh": ["D020246"], "umls": ["C0149871"], "icd-9": ["453"], "icd-10": ["I80", "I82"], "wikidata": ["Q2751330"]}
Cutis rhomboidalis nuchae SpecialtyDermatology Cutis rhomboidalis nuchae is a skin condition of the posterior neck, characterized by deep furrowing of the skin.[1] ## See also[edit] * List of cutaneous conditions * Poikiloderma of Civatte * Solar elastosis ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. ## External links[edit] Classification D * ICD-10: L57.2 * v * t * e Radiation-related disorders / Photodermatoses Ultraviolet/ionizing * Sunburn * Phytophotodermatitis * Solar urticaria * Polymorphous light eruption * Benign summer light eruption * Juvenile spring eruption * Acne aestivalis * Hydroa vacciniforme * Solar erythema Non-ionizing Actinic rays * Actinic keratosis * Atrophic actinic keratosis * Hyperkeratotic actinic keratosis * Lichenoid actinic keratosis * Pigmented actinic keratosis * Actinic cheilitis * Actinic granuloma * Actinic prurigo * Chronic actinic dermatitis Infrared/heat * Erythema ab igne (Kangri ulcer * Kairo cancer * Kang cancer * Peat fire cancer) * Cutis rhomboidalis nuchae * Poikiloderma of Civatte Other * Radiation dermatitis * Acute * Chronic radiodermatitis) * Favre–Racouchot syndrome * Photoaging * Photosensitivity with HIV infection * Phototoxic tar dermatitis This dermatology article is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Cutis rhomboidalis nuchae	c0263416	3,917	wikipedia	https://en.wikipedia.org/wiki/Cutis_rhomboidalis_nuchae	2021-01-18T18:55:22	{"umls": ["C0263416"], "icd-10": ["L57.2"], "wikidata": ["Q5196859"]}
## Summary ### Clinical characteristics. Lymphedema-distichiasis syndrome (referred to as LDS in this GeneReview) is characterized by lower-limb lymphedema, and distichiasis (aberrant eyelashes ranging from a full set of extra eyelashes to a single hair). Lymphedema typically appears in late childhood or puberty, is confined to the lower limbs with or without involvement of the external genitalia, and is often asymmetric; severity varies within families. Males develop edema at an earlier age and have more problems with cellulitis than females. Distichiasis, which may be present at birth, is observed in 94% of affected individuals. About 75% of affected individuals have ocular findings including corneal irritation, recurrent conjunctivitis, and photophobia; other common findings include varicose veins and ptosis. ### Diagnosis/testing. The clinical diagnosis of LDS is established in a proband with either lymphedema and distichiasis, distichiasis and a family history of lower-limb lymphedema, or lower-limb lymphedema and a family history of distichiasis. If clinical findings are not diagnostic, the identification of a heterozygous FOXC2 pathogenic variant by molecular genetic testing confirms the diagnosis. ### Management. Treatment of manifestations: Lubrication, plucking, cryotherapy, electrolysis, or lid splitting for treatment of distichiasis; fitted compression garments and bandaging to improve swelling and discomfort associated with edema. To prevent secondary cellulitis, good skin care and prompt treatment of infected skin lesions; prompt treatment of cellulitis with antibiotics. The implementation of hosiery prior to the development of lymphedema may help reduce the extent of edema. Diuretics are not effective in the treatment of lymphedema. ### Genetic counseling. LDS is inherited in an autosomal dominant manner. Approximately 75% of affected individuals have an affected parent; about 25% have a de novo pathogenic variant. Each child of an individual with LDS has a 50% chance of inheriting the pathogenic variant. Disease severity cannot be predicted and is variable even within the same family. If the FOXC2 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. Fetal echocardiography is recommended because of the increased risk for congenital heart disease, renal abnormalities, cleft palate, and hydrothoraces or hydrops fetalis. ## Diagnosis ### Suggestive Findings Lymphedema-distichiasis syndrome (LDS) should be suspected in individuals with the following clinical findings: * Primary lymphedema (chronic swelling of the extremities caused by an intrinsic dysfunction of the lymphatic vessels) typically affecting the lower limbs ± genitalia with onset in late childhood or puberty * Distichiasis (aberrant, extra eyelashes arising from the meibomian glands on the inner aspects of the inferior and/or superior eyelids, ranging from a full set of extra eyelashes to a single hair * Varicose veins in the lower limbs presenting at puberty or early adulthood * Ptosis (drooping upper eyelid) of one or both eyes * Other less frequent findings: * Congenital heart disease including bicuspid aortic valves * Cleft palate ± Pierre Robin sequence * Renal anomalies * Spinal extradural arachnoid cysts * Nonimmune hydrops fetalis * Antenatal hydrothoraces * Neck webbing ### Establishing the Diagnosis The clinical diagnosis of LDS is established in a proband with one of the following: * Distichiasis and lymphedema (although a young child may have no evidence of lymphedema) * Distichiasis and a family history of lower-limb lymphedema * Lower-limb lymphedema and a family history of distichiasis If clinical findings are not diagnostic, the identification of a heterozygous pathogenic variant in FOXC2 by molecular genetic testing can confirm the diagnosis (see Table 1). Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of LDS can be specific to this condition, individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of LDS has not been considered are more likely to be diagnosed using genomic testing (see Option 2). #### Option 1 When the phenotypic findings suggest the diagnosis of LDS, molecular genetic testing approaches can include single-gene testing or use of a multigene panel: * Single-gene testing. Sequence analysis of FOXC2 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. * A primary lymphedema multigene panel that includes FOXC2 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here. #### Option 2 When the diagnosis of LDS is not considered because an individual has atypical phenotypic 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 the most commonly used genomic testing method; genome sequencing is also possible. If exome sequencing is not diagnostic, exome array (when clinically available) may be considered to detect (multi)exon deletions or duplications that cannot be detected by sequence analysis. For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here. ### Table 1. Molecular Genetic Testing Used in Lymphedema-Distichiasis Syndrome View in own window Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method FOXC2Sequence analysis 3~95% Gene-targeted deletion/duplication analysis 4Unknown; none reported 5 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\. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. 5\. No data on detection rate of gene-targeted deletion/duplication analysis are available. ## Clinical Characteristics ### Clinical Description Lymphedema-distichiasis syndrome (LDS) is characterized by lymphedema with onset in late childhood or puberty and is confined to the lower limbs and/or genitalia. Varicose veins are a frequent association and may develop before the onset of the lymphedema. Distichiasis, which may be present at birth, can be associated with ocular problems such as corneal irritation, recurrent conjunctivitis, and photophobia. Congenital ptosis involving one or both eyes may be present. Other less common findings include congenital heart disease, cleft palate, webbed neck, and renal anomalies. Severity varies within and between families, with some affected neonates presenting with hydrops fetalis. Lymphedema is present in most individuals with LDS. While it typically appears in late childhood or puberty (age range: 7-40 years) [Erickson et al 2001, Brice et al 2002], congenital onset has been reported [Finegold et al 2001]. In females, pregnancy or use of oral contraceptives may precipitate the onset of swelling. Lymphedema is confined to the lower limbs, is often asymmetric, and can be unilateral. The severity of the lymphedema varies within families. Males develop edema at a significantly earlier age and have more problems with cellulitis than females. Sixty-five percent of males in one series complained of recurrent cellulitis in the edematous leg, compared to 25% of females [Brice et al 2002]. Whereas primary lymphedema is usually associated with hypoplasia or aplasia of the lymphatic vessels, LDS is associated with an increased number of lymphatic vessels and inguinal lymph nodes [Dale 1987, Brice 2003]. The valves in the lymphatic vessels and veins are small and dysplastic, resulting in reflux and edema [Petrova et al 2004]. Isotope lymphoscintigraphy can be used to demonstrate that the swelling is caused by lymphedema. Radioactive colloid is injected into the toe web spaces and uptake in the ilioinguinal nodes is measured at intervals. Low uptake can be demonstrated in most affected individuals in association with dermal backflow, indicating lymph reflux into the lower limbs. This technique replaces lymphangiography (x-ray after injection of dye into the lymphatic vessels in the foot). Distichiasis describes the presence of aberrant eyelashes arising from the meibomian glands on the inner aspects of the inferior and superior eyelids. These range from a full set of extra eyelashes to a single hair. Distichiasis is observed in 94% of individuals with LDS [Brice et al 2002]. Although distichiasis may be present at birth, it may not be recognized until early childhood. About 75% of affected individuals have ocular problems related to distichiasis, including corneal irritation, recurrent conjunctivitis, and photophobia. About 25% of individuals have no symptoms from distichiasis and are thus not aware of it. Therefore, any individual with primary lymphedema of the lower limbs should be examined carefully for the presence of distichiasis. Finegold et al [2001] described one family with a FOXC2 pathogenic variant with lymphedema only; however, only three individuals were affected and it is not known whether they were examined by slit lamp for evidence of distichiasis, which can sometimes be very subtle. In a study of 23 probands reported to have Meige disease (see Differential Diagnosis) only one had a pathogenic variant in FOXC2. More extensive examination of the individuals in this family revealed that although the proband did not have distichiasis, four affected relatives had evidence of distichiasis on slit lamp examination [Rezaie et al 2008]. In one family, distichiasis was associated with a pathogenic variant in FOXC2 but none of the affected individuals had evidence of lymphedema. The two affected individuals in the family were the 13-year-old proband (in whom lymphedema could still develop) and her father [Brooks et al 2003]. Varicose veins. The incidence of varicose veins is much higher (and onset earlier) in individuals with LDS than in the general population. About 50% of individuals with LDS have clinically evident varicose veins [Brice et al 2002]. In one family, light-reflective rheography and Doppler studies showed bilateral incompetence at the sapheno-femoral junction and long saphenous vein, which were presumed to be congenital abnormalities affecting both deep and superficial veins [Rosbotham et al 2000]. Ongoing studies of venous abnormalities suggest that they are present in all individuals with FOXC2 pathogenic variants [Mellor et al 2007]. FOXC2 is essential for lymphatic and venous valve formation in the embryo [Lyons et al 2017]. Ptosis. Approximately 30% of individuals with LDS have unilateral or bilateral congenital ptosis of variable severity. Congenital heart disease occurs in 7%-10% of individuals with LDS. Structural abnormalities include ventricular septal defect, atrial septal defect, patent ductus arteriosis, bicuspid aortic valve, and tetralogy of Fallot. Cardiac arrhythmia, most commonly sinus bradycardia, may also occur. Cleft palate. About 4% of individuals have cleft palate with or without Pierre Robin sequence [Papoff et al 2016]. Other findings * Nonimmune hydrops fetalis or antenatal hydrothoraces have been reported as a rare complication of LDS. Hydrops fetalis can be caused by lymphatic abnormalities [Bellini et al 2015]. If the fetus or neonate survives, the hydrops may resolve completely. It has been suggested that the hydrops and respiratory failure may be due to severe pulmonary lymphangiectasia [de Bruyn et al 2012, Sargent et al 2014]. * Spinal extradural arachnoid cyst (SEDAC) is a cyst in the spinal canal that protrudes into the epidural space from a defect in the dura mater. Thus, SEDAC caused by a heterozygous FOXC2 loss-of-function variant should be considered a feature of LDS. It may manifest as the sole finding, but more frequently the family history is positive for SEDAC, distichiasis, and/or lymphedema [Kanaan et al 2006, Ogura et al 2013]. * Renal anomalies include hydronephrosis, ectopic kidney, and renal agenesis, which may be detected by antenatal ultrasound examination [Jones et al 2017]. Other abnormalities include scoliosis, neck webbing, uterine anomalies, strabismus, and synophrys. Neonatal chylothorax has been reported in one case in association with congenital heart disease [Chen et al 1996]. One paper suggested an association with yellow nails, but discolored nails are a common feature of chronic lymphedema regardless of cause. ### Genotype-Phenotype Correlations No genotype-phenotype correlations for the major clinical signs have been reported. ### Penetrance Approximately 80% of individuals with lymphedema-distichiasis syndrome have lymphedema by early adulthood (age 30 years), although a few individuals may develop lymphedema later. Approximately 94% of affected individuals have distichiasis. In all families with FOXC pathogenic variants reported, at least one individual has had distichiasis. ### Nomenclature Lymphedema and ptosis, once described as a separate entity, is thought to be the same as lymphedema-distichiasis syndrome [Finegold et al 2001]. ### Prevalence The prevalence of lymphedema-distichiasis syndrome is not known; it is a well-recognized and relatively frequent cause of autosomal dominant primary lymphedema. ## Differential Diagnosis ### Table 2. Disorders to Consider in the Differential Diagnosis of Lymphedema-Distichiasis Syndrome (LDS) View in own window DiffDx DisorderGene(s)MOIClinical Features of DiffDx Disorder Overlapping w/LDSDistinguishing from LDS Milroy diseaseFLT4ADLymphedema 1 * Typically congenital-onset lymphedema (very rarely presents later) * Absence of distichiasis Meige disease (OMIM 153200)UnknownAD * Absence of distichiasis Hypotrichosis-lymphedema-telangiectasia syndrome (OMIM 607823)SOX18AR * Loss of hair * Telangiectasia, particularly in the palms * Absence of distichiasis Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome (OMIM 137940)AD Lymphedema microcephaly (OMIM 152950)KIF11AD * Small head circumference * May be associated w/chorioretinopathy &/or ID * Absence of distichiasis Yellow nail syndrome (OMIM 153300)UnknownAD 2 * Very slow-growing nails w/transverse overcurvature & hardening of the nail plate 3 * Absence of distichiasis Emberger syndrome (OMIM 614038)GATA2AD * Myelodysplasia * Immunodeficiency * Absence of distichiasis Blepharocheilodontic syndrome (OMIM PS119580)CDH1 CTNND1ADDistichiasis 4 * Lagophthalmos (inability to fully close eyes) * Cleft lip & palate * Atrial septal defect * Oligodontia * Absence of lymphedema AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked 1\. The presence of lymphatic vessels on lymphoscintigraphy in LDS contrasts with other causes of primary lymphedema, including Milroy disease and Meige disease, which show aplasia or hypoplasia of the lymphatic vessels. 2\. Inheritance is said to be autosomal dominant; most affected individuals represent simplex cases (i.e., a single occurrence in a family) [Hoque et al 2007]. 3\. Nail changes are different from the typically discolored nails often associated with chronic lymphedema. 4\. Distichiasis should also be clinically distinguished from trichiasis, a more common condition in which lashes arise normally from the anterior lamella of the eyelids but are misdirected. The misdirected lashes can cause symptoms similar to distichiasis (e.g., corneal irritation and photophobia). ## Management ### Evaluations Following Initial Diagnosis To establish the extent of disease and needs of in an individual diagnosed with lymphedema-distichiasis syndrome (LDS), the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended. ### Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Lymphedema-Distichiasis Syndrome View in own window System/ ConcernEvaluationComment EyesOphthalmologic eval * Slit lamp eval for distichiasis & related problems of corneal irritation, recurrent conjunctivitis, & photophobia * Assess for ptosis. * Assess for strabismus. LymphedemaPhysical exam of lower legs to document presence of lymphedema & any evidence of cellulitisIsotope lymphoscintigraphy to detect lymphatic weakness before onset of swelling VascularPhysical exam of varicose veins w/young onset (adolescence / early adulthood)Venous duplex scans Cleft palateAssess for cleft palate or Pierre Robin sequence. CardiovascularAssess for congenital heart defects. * Echocardiogram * Further eval if clinical evidence suggests arrhythmias SpineAssess for spinal extradural arachnoid cyst. * Cysts can result in fluctuating symptoms (e.g., when enlarged, they may compress the root or cord & result in pain or weakness). * Spinal MRI if symptomatic Assess for scoliosis. RenalRenal ultrasound evalAssess for renal anomalies. Miscellaneous/ OtherConsultation w/clinical geneticist &/or genetic counselor ### Treatment of Manifestations Eyes * Conservative management of symptomatic distichiasis with lubrication or epilation (plucking), or more definitive management with cryotherapy, electrolysis, or lid splitting [O'Donnell & Collin 1993]. Recurrence is possible even with more definitive treatment. * Surgery for ptosis if clinically indicated (e.g., obscured vision, cosmetic appearance) Lymphedema. Refer to a lymphedema therapist for management of edema (fitting hosiery, massage). Although the edema cannot be cured, some improvement may be possible with the use of carefully fitted hosiery and/or bandaging, which may reduce the size of the swelling as well as the associated discomfort. The implementation of hosiery prior to the development of lymphedema may be beneficial in reducing the extent of edema [P Mortimer, personal communication]. The following are appropriate: * Prevention of secondary cellulitis in areas with lymphedema, particularly as cellulitis may aggravate the degree of edema. Prophylactic antibiotics (e.g., penicillin V 500 mg/day) are recommended for recurrent cellulitis. * Prompt treatment of early cellulitis with appropriate antibiotics. It may be necessary to give the first few doses intravenously if there is severe systemic upset. * Prevention of foot infections (particularly athlete's foot / infected eczema) by treatment with appropriate creams/ointments Note: (1) Diuretics are not effective in the treatment of lymphedema. (2) Cosmetic surgery is often associated with disappointing results. See fact sheet for more information. Varicose veins. Manage varicose veins conservatively with compression garments if possible, as surgery could aggravate the edema and increase the risk of infection or cellulitis. Cardiac anomalies/arrhythmia. Manage as per standard practice. Spine * Spinal extradural arachnoid cyst. Refer individuals with symptomatic spinal cysts (i.e., any neurologic signs or symptoms, especially in the lower limbs) to a neurosurgeon. * Scoliosis. Standard treatment Renal malformations. Standard treatment ### Surveillance ### Table 4. Recommended Surveillance for Individuals with Lymphedema-Distichiasis Syndrome View in own window System/ConcernEvaluationFrequency EyesSlit lamp exam of the eyesAs required for control of symptoms from distichiasis LymphedemaLymphoscintigraphy at diagnosis, then clinical assessment1-2x/yr, but regular lymphedema therapy (every 6 mos) 1 Varicose veinsClinical assessment1-2x/yr Cleft palatePer craniofacial team CardiovascularPer cardiologist SpineInvestigate w/spine MRI; only if symptomatic. RenalPer treating nephrologist/urologist 1\. See fact sheet for more information. ### Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. ### Pregnancy Management Edema may be exacerbated during pregnancy, but often improves after delivery. The patient should continue compression and bandage treatment as long as possible but this should be adapted to the patient's needs (e.g., thigh-length compression garments instead of tights). See fact sheet for more information. ### Therapies Under Investigation Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. 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	Lymphedema-Distichiasis Syndrome	c0265345	3,918	gene_reviews	https://www.ncbi.nlm.nih.gov/books/NBK1457/	2021-01-18T21:14:19	{"mesh": ["C537710"], "synonyms": []}
Spondylosis deformans Patient with spondylosis deformans Spondylosis deformans is a disease of spine in humans and other vertebrates. It occurs when intervertebral discs begin to degenerate, leading to the formation of bony spurs or bridges around the disc and nearby spinal joints. Severe cases can result in pressure on the spinal nerves, causing neurological signs and symptoms.[1] Other terms for the disease have included spondylitis, but this is incorrect because it implies that the condition is inflammatory in nature, like ankylosing spondylitis.[1] The condition is likely triggered by changes in the anulus fibrosus, the tough outer ring of the intervertebral disc. This disc degeneration causes osteophytes to grow in the area. The osteophytes develop bridges of connective tissue which become ossified, forming bone spurs. The pattern of osteophyte formation varies. The exact pathophysiology of the process is unclear.[1] ## References[edit] 1. ^ a b c Newton, C. D. and Nunamaker, D. M. Chapter 61: Spondylosis Deformans. Textbook of Small Animal Orthopaedics. J. B. Lippincott Company. 1985. * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Spondylosis deformans	c0038020	3,919	wikipedia	https://en.wikipedia.org/wiki/Spondylosis_deformans	2021-01-18T19:06:23	{"mesh": ["D055009"], "umls": ["C0038020"], "wikidata": ["Q48834903"]}
A number sign (#) is used with this entry because of evidence that susceptibility to age-related macular degeneration-13 (ARMD13) is conferred by heterozygous mutation in the CFI gene (217030) on chromosome 4q25. Description Age-related macular degeneration (ARMD) is a multifactorial disorder of the central retina that is the most prevalent cause of progressive vision loss in the developed world. As in other chronic age-related diseases, most cases result from interplay between multiple environmental and genetic factors, with a resultant spectrum of phenotypes. In rare cases, ARMD may manifest early, but there is an exponential rise in prevalence after the age of 60 years (summary by Pras et al., 2015). For a phenotypic description and a discussion of genetic heterogeneity of age-related macular degeneration (ARMD), see 603075. Clinical Features Pras et al. (2015) studied 2 Tunisian Jewish families in which affected individuals manifested a severe, highly penetrant phenotype of early-onset macular degeneration, with retinal pathologies that were indistinguishable from common ARMD, and high rates of advancement to blindness at senility. In the first family, 2 Tunisian Jewish sisters with ARMD, aged 66 and 68 years, showed distinct mechanisms of macular destruction and vision loss. One sister developed choroidal neovascularization that responded poorly to treatment, whereas the other sister showed progressive retinal pigment epithelium (RPE) loss and geographic atrophy, with surrounding well-defined hard drusen. Neither sister smoked; however, exome analysis (see MOLECULAR GENETICS) revealed differences in genetic background that might account for their disparate features. An unrelated 24-year-old Tunisian Jewish man, who presented with a conjunctival foreign body, was found on examination to have widespread intermediate ARMD, with multiple small foveal drusen and larger confluent drusen temporally. His affected mother and 3 of her sibs, who were in their fifth and sixth decades of life, showed dry (nonneovascular) ARMD with features that were less prominent than those of the proband. His maternal grandmother, who was blind at age 74, exhibited a wet (exudative) form of ARMD. Pras et al. (2015) noted that the proband had a 10-year history of smoking, a well-established risk factor for ARMD, which might explain the early onset of his disease. Mapping In a case-control study involving 1,228 unrelated Caucasian patients aged 60 years or older with dry or neovascular advanced age-related macular degeneration and 825 controls, Fagerness et al. (2009) analyzed 1,500 SNPs in complement pathway genes and previously studied regions of interest, and identified significant association with 2 SNPs on chromosome 4q25, rs13117504 and rs10033900 (p = 2.11 x 10(-7) and 6.46 x 10(-8), respectively); the 2-SNP haplotype showed slightly stronger association than either SNP alone (p = 1.18 x 10(-8)). No obvious functional variation was found in coding exons in linkage disequilibrium with the SNPs. Fagerness et al. (2009) concluded that these SNPs likely tag an undiscovered biologically relevant variant. Molecular Genetics In 84 unrelated patients with ARMD, van de Ven et al. (2013) analyzed the candidate gene CFI (217030) and identified 2 heterozygous missense mutations: G119R (217030.0010) in 3 probands, and G188A in 1 proband and 3 affected family members. Neither mutation was found in 192 ancestry- and age-matched controls, and no coexisting mutations in CFH (134370) were detected in patients carrying the CFI G119R or G188A substitutions. The G188A mutation was not found in 809 unrelated ARMD cases; however, screening for the G119R variant in 1,014 ARMD cases and 711 controls revealed the variant in 11 additional cases but none of the controls, demonstrating strong association of the G119R variant with ARMD (p = 2.16 x 10(-4)). Genotyping for G119R in additional cases resulted in the variant being identified in an overall total of 20 of 3,567 cases versus only 1 of 3,937 controls, consistent with G119R conferring high risk for developing ARMD (odds ratio, 22.20; p = 3.79 x 10(-6)). Van de Ven et al. (2013) noted that most carriers of the G119R variant had stage 4 ARMD. The 1 control carrying the minor allele had numerous hard drusen in all 4 quadrants of the peripheral retina but a normal macula in both eyes. Van de Ven et al. (2013) also noted that the G119R variant had previously been reported in patients with atypical hemolytic uremia syndrome (AHUS3; 612923) (Maga et al., 2010; Fakhouri et al., 2010); however, although ARMD patients carrying the CFI G119R variant exhibited a mild subclinical decrease in renal function, there was no significant difference in renal function of ARMD patients with G119R compared to ARMD patients without G119R. Seddon et al. (2013) sequenced the exons of 681 genes within all reported ARMD loci and related pathways in 2,493 cases. First, each gene was tested for increased or decreased burden of rare variants in cases compared to controls. Seddon et al. (2013) found that 7.8% of ARMD cases compared to 2.3% of controls were carriers of rare missense CFI variants (odds ratio = 3.6; p = 2 x 10(-8)). There was a preponderance of dysfunctional variants in cases compared to controls. Seddon et al. (2013) then tested individual variants for association with disease. To evaluate the functional impact of rare variants in the CFI gene, Kavanagh et al. (2015) measured circulating serum factor I (FI) protein levels in individuals with and without rare CFI variants. They observed that individuals with advanced ARMD carrying a rare CFI variant had lower mean FI than controls carrying a variant (p less than 0.001), and that individuals with a CFI rare variant and low FI were more likely to have advanced ARMD (p = 5.6 x 10(-5)). Controlling for covariates, low FI increased the risk of advanced ARMD among those with a variant compared to carrier individuals without advanced ARMD (OR 13.6; p = 1.6 x 10(-4)) and compared to controls without a rare CFI variant (OR 19.0; p = 1.1 x 10(-5)). By whole-exome sequencing of 2 Tunisian Jewish sisters with ARMD, Pras et al. (2015) identified heterozygosity for a missense mutation in the CFI gene (V412M; 217030.0011) that segregated with disease in the family. Screening of 12 unrelated Tunisian patients with ARMD identified another carrier of the V412M mutation, a 24-year-old Jewish man; the mutation segregated fully with ARMD in his family as well. Analysis of 200 unrelated Tunisian Jewish controls identified 10 heterozygotes, for an estimated carrier frequency of 5% in that population. linkage analysis for V412M and ARMD in the 2 families yielded a lod score of 2.51 (theta = 0), strongly suggesting the CFI mutation as the cause of disease. Because the 2 affected sisters from the first family exhibited distinct mechanisms of macular destruction, with 1 showing choroidal neovascularization and the other geographic atrophy of the RPE, Pras et al. (2015) compared their exome data and identified some genetic background differences, including disparity in the ARMS2 gene (611313): the sister who developed CNV exclusively carried 2 heterozygous ARMS2 changes, R38X (rs2736911) and A69S (rs10490924; 611313.0001). The authors noted that the latter variant is regarded as an established risk factor for the wet form of ARMD. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Macular degeneration, age-related \- Progressive vision loss \- Multiple drusen of variable size \- Retinal pigment epithelium (RPE) atrophy (in some patients) \- Atrophic macular degeneration, early onset \- Macular scarring (cicatricial AMD) \- Choroidal neovascularization (in some patients) \- Late hyperfluorescence on fluorescein angiography, attributed to choroidal neovascularization \- 'Starry sky' staining of basal laminar drusen on fluorescein angiography \- Accumulation of fluid under RPE and subretinally on optical coherence tomography, attributed to choroidal neovascularization GENITOURINARY Kidneys \- Mild subclinical decrease in renal function MISCELLANEOUS \- Early onset of symptoms \- Disease steadily progressive \- 'Dry' AMD seen in most patients, however an exudative 'wet' appearance was observed in the oldest patient from 1 family (examined at age 74) MOLECULAR BASIS \- Susceptibility conferred by mutation in the complement factor I gene (CFI, 217030.0010 ) ▲ 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	MACULAR DEGENERATION, AGE-RELATED, 13	c3809523	3,920	omim	https://www.omim.org/entry/615439	2019-09-22T15:52:27	{"omim": ["615439"]}
A number sign (#) is used with this entry because autosomal dominant mental retardation-18 (MRD18) is caused by heterozygous mutation in the GATAD2B gene (614998) on chromosome 1q21. Description Autosomal dominant mental retardation-18 is characterized by severe intellectual disability, limited language development, motor delay, and dysmorphic features, including hypertelorism and narrow palpebral fissures (summary by Luo et al., 2017). Clinical Features De Ligt et al. (2012) reported a girl (patient 69) with global developmental delay who learned to walk at 3 years and had a few single words at age 8. She had tics, high pain threshold, and hypoplasia of the optic nerve. At 34 years of age, she had severe intellectual disability and strabismus and made grimaces. Height and head circumference were normal. Facial characteristics included thin blonde hair, deeply set eyes, tubular nose with a broad nasal tip, and a large mouth with a thin upper lip. The woman was found to have a mutation in the GATAD2B gene. De Ligt et al. (2012) screened a second cohort of 765 individuals with intellectual disability and identified a second mutation in GATAD2B in a patient with severe developmental delay with delayed motor milestones, limited speech, and overlapping facial features. Willemsen et al. (2013) reported a girl with developmental delay and similar dysmorphic features as the patients reported by de Ligt et al. (2012). The patient was hypotonic in the neonatal period and thereafter showed delayed psychomotor development. She learned to walk at age 2 years and started to speak during the third year, but only spoke 6 words at age 12 years. Her behavior was characterized by hyperactivity, inappropriate laughter, obsession for shiny objects, and mild self-mutilation. She also had strabismus and hypermetropic astigmatism. Facial dysmorphism included a broad forehead, a broad nasal bridge with full nose tip, a broad mouth with wide-spaced central incisors, short philtrum, and long palpebral fissures. She had thin, blond hair. Her fingers were long and she had fleshy hands. Luo et al. (2017) reported 2 unrelated Chinese children with severe mental retardation. One child had hypertelorism, downward slanting palpebral fissures, and flat nasal bridge. At age 4 years, he could not walk stably. At age 11, he could speak only a few words and could walk but not run normally. The other child, born full-term to nonconsanguineous parents, had small palpebral fissures, hypertelorism, a flat, low nasal bridge, and dental misalignment. She sat at age 10 months, stood at age 1 year, and walked at age 2. At age 9, she had hyperactivity. At age 12, she could not speak any words; she could run and play alone and eat independently, but could not wash her face. Cytogenetics Willemsen et al. (2013) reported a girl with intellectual disability associated with a de novo heterozygous 249-kb deletion of chromosome 1q21.3 encompassing 10 genes and disrupting GATAD2B. No other known disease-related genes were in the deleted region. The girl had hypotonia and feeding difficulties in the neonatal period, followed by delayed psychomotor development and poor speech. Medical problems included hypermetropia and strabismus, and she had 1 episode of absence epilepsy. Facial dysmorphism included hypertelorism, a broad forehead, a broad and flat nasal bridge, and a full square tip of the nose. She had thin, blond hair. Molecular Genetics In 2 patients with severe intellectual disability and similar dysmorphic features, de Ligt et al. (2012) identified heterozygous de novo mutations in the GATAD2B gene: a nonsense mutation (Q470X; 614998.0001) and a frameshift mutation (614998.0002). In a patient with intellectual disability and dysmorphic features, Willemsen et al. (2013) identified a heterozygous truncating mutation in the GATAD2B gene (614998.0003). Her unaffected mother carried the mutation in mosaic state (10% in peripheral blood leukocytes). The patient was identified from a larger cohort of 80 patients with similar features who were screened for mutations in the GATAD2B gene. In 2 patients with severe intellectual disability, limited language development, and dysmorphic features, Luo et al. (2017) identified heterozygous de novo frameshift mutations in the GATAD2B gene (614998.0004-614998.0005). The mutations were identified by a next-generation sequencing panel targeting genes associated with intellectual disability. Western blot analysis revealed a reduction in the GATAD2B protein in lymphoblasts from both individuals compared with normal controls. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Broad forehead \- Short philtrum Eyes \- Strabismus \- Hypermetropia \- Narrow palpebral fissures \- Hypertelorism \- Deep-set eyes Nose \- Tubular nose \- Broad nasal bridge Mouth \- Broad mouth \- Thin upper lip SKELETAL Hands \- Long fingers Feet \- Long toes MUSCLE, SOFT TISSUES \- Hypotonia, neonatal NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Intellectual disability \- Poor speech Behavioral Psychiatric Manifestations \- Hyperactivity (in some patients) \- Tics (in some patients) \- Easy frustration (in some patients) MISCELLANEOUS \- Onset in infancy \- Three unrelated patients have been reported (last curated September 2013) MOLECULAR BASIS \- Caused by mutation in the GATA zinc finger domain-containing protein 2B gene (GATAD2B, 614998.0001 ) ▲ 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	MENTAL RETARDATION, AUTOSOMAL DOMINANT 18	c3554448	3,921	omim	https://www.omim.org/entry/615074	2019-09-22T15:53:15	{"doid": ["0070048"], "omim": ["615074"], "orphanet": ["363686"], "synonyms": []}
A number sign (#) is used with this entry because HID syndrome is caused by heterozygous mutation in the GJB2 gene (121011), which is also mutant in KID syndrome (148210), on chromosome 13q12. Clinical Features Schnyder and Gloor (1977) and Gulzow and Anton-Lamprecht (1977) described a 17-year-old male with ichthyosis hystrix and bilateral hearing loss. Thereafter, sporadic cases of both sexes were reported (Baden and Bronstein, 1988; Badillet et al., 1982). Because of characteristic electron microscopic features, the disease was considered a distinct entity and was initially named 'ichthyosis hystrix gravior, type Rheydt' after the city of origin of the patient, located near Dusseldorf, Germany. Traupe (1989) suggested the designation hystrix-like ichthyosis with deafness, or HID syndrome. The disease became manifest shortly after birth with erythematous patches. At the age of 1 year, spiky and cobblestone-like hyperkeratotic masses involved the entire skin. The palms and soles were only mildly affected. Scarring alopecia also occurred. Histopathologic features resembled those of lamellar ichthyosis and were not diagnostic. Ultrastructural changes included excess formation of mucous-containing granules and reduction of tonofibrils. Konig et al. (1997) reported the first instance of familial occurrence. The 3-month-old son of the patient reported in 1977 had neurosensory deafness and typical cutaneous involvement, including red hyperkeratotic papules on the face and disseminated induration of the entire skin with diffuse dark-yellow hyperkeratoses. An important differential diagnosis of HID syndrome is KID syndrome (keratitis, ichthyosis-like hyperkeratosis, and deafness), of which both autosomal dominant (148210) and autosomal recessive (242150) forms may exist. KID syndrome does not represent a true form of ichthyosis, however, but rather a particular type of erythrokeratodermia and can be differentiated from the HID syndrome by a number of features. Although both conditions show neurosensory deafness and proneness to bacterial and mycotic skin infections, the skin changes in KID syndrome may be present at birth in the form of hyperkeratotic erythroderma that resolves spontaneously. Later on, hyperkeratotic plaques recur but they never involve the trunk. The palms and the soles are severely affected, which represents a feature different from the HID phenotype. Moreover, the electron microscopic features observed in the 2 syndromes are different. Van Geel et al. (2002) provided photographs of the first reported patient with HID syndrome (Schnyder and Gloor, 1977; Gulzow and Anton-Lamprecht, 1977). Extensive spiky hyperkeratosis covered most of the skin of the face and neck with a slightly erythrodermic aspect. Cobblestone-like hyperkeratosis was present on the scalp. Hypotrichosis of eyebrows, eyelids, and scalp was likewise present. Erythroderma and impressive cobblestone-like hyperkeratosis around the knees changed abruptly into a spiky hyperkeratosis in some areas. Molecular Genetics Because of similarities between HID syndrome and KID syndrome, which results from mutations in the connexin-26 gene (GJB2), van Geel et al. (2002) searched for mutations in the GJB2 gene in the first reported case of HID syndrome (Schnyder and Gloor, 1977; Gulzow and Anton-Lamprecht, 1977). They extracted DNA from paraffin-embedded tissue samples. Since the KID syndrome mutation, asp50 to asn (121011.0020), abolished an AspI restriction site, they analyzed this site by PCR and restriction digestion and demonstrated that the HID patient was heterozygous for lack of the restriction site. Subsequently, they confirmed the presence of the mutation by direct sequencing and found no additional variations in the GJB2 gene. Van Geel et al. (2002) concluded that KID syndrome and HID syndrome are identical at the molecular level and represent a single clinical entity. INHERITANCE \- Autosomal dominant HEAD & NECK Ears \- Deafness, sensorineural Eyes \- Absent eyelashes SKELETAL Feet \- Pes cavus SKIN, NAILS, & HAIR Skin \- Spiky hyperkeratosis \- Erythroderma \- Punctate keratitis \- Ichthyosis \- Variable involvement of palms and soles Hair \- Absent-sparse eyelashes \- Sparse eyebrows \- Scarring alopecia NEOPLASIA \- Squamous cell carcinoma MISCELLANEOUS \- Allelic to KID syndrome ( 148210 ), DFNA3 ( 601544 ), DFNB1 ( 220290 ), Vohwinkel syndrome ( 124500 ), keratoderma, palmoplantar with deafness ( 148350 ) \- KID syndrome and HID syndrome are identical at the molecular level \- Onset in first year of life MOLECULAR BASIS \- Caused by mutation in the connexin 26 gene (GJB2, 121011.0020 ) ▲ 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	ICHTHYOSIS, HYSTRIX-LIKE, WITH DEAFNESS	c3665333	3,922	omim	https://www.omim.org/entry/602540	2019-09-22T16:13:37	{"mesh": ["C580224"], "omim": ["602540"], "orphanet": ["477"], "synonyms": ["Alternative titles", "HID SYNDROME"]}
Pregnancy-induced hypertension Micrograph showing hypertrophic decidual vasculopathy, the histomorphologic correlate of gestational hypertension. H&E stain. SpecialtyObstetrics Gestational hypertension or pregnancy-induced hypertension (PIH) is the development of new hypertension in a pregnant woman after 20 weeks' gestation without the presence of protein in the urine or other signs of pre-eclampsia.[1] Gestational hypertension is defined as having a blood pressure greater than 140/90 on two separate occasions at least 6 hours apart.[1] ## Contents * 1 Signs and symptoms * 2 Risk factors * 3 Diagnosis * 3.1 Conditions * 4 Treatment * 5 Evolutionary considerations * 5.1 Humans * 5.2 Origins of the placenta * 5.3 Incorrect placental implantation * 5.4 Evolutionary tradeoff * 5.5 Relevance of evolutionary history * 6 References * 7 External links ## Signs and symptoms[edit] No single diagnostic test currently exists to predict the likelihood of developing gestational hypertension. High blood pressure is the major sign in diagnosing gestational hypertension. Some women with gestational hypertension may present asymptomatic, but a number of symptoms are associated with the condition.[1] Symptoms * Edema * Sudden weight gain * Blurred vision or sensitivity to light * Nausea and vomiting * Persistent headaches * Increased blood pressure ## Risk factors[edit] Maternal causes * Obesity * Mothers under 20 or over 40 years old[2] * Past history of diabetes mellitus, hypertension (particularly gestational hypertension) and renal disease[2] * Pre-existing hypertension[2] * Thrombophilias (anti-phospholoipid syndrome, protein C/S deficiency, factor V Leiden) * Having donated a kidney[3] Pregnancy * Multiple gestation (twins or triplets, etc.)[2] * Placental abnormalities: * Hyperplacentosis: Excessive exposure to chorionic villi * Placental ischemia Family history * Family history of pre-eclampsia ## Diagnosis[edit] ### Conditions[edit] There exist several hypertensive states of pregnancy: Gestational hypertension Gestational hypertension is usually defined as having a blood pressure higher than 140/90 measured on two separate occasions, more than 6 hours apart, without the presence of protein in the urine and diagnosed after 20 weeks of gestation.[4] Pre-eclampsia Pre-eclampsia is gestational hypertension plus proteinuria (>300 mg of protein in a 24-hour urine sample). Severe pre-eclampsia involves a blood pressure greater than 160/110, with additional medical signs and symptoms. HELLP syndrome is a type of pre-eclampsia. It is a combination of three medical conditions: hemolytic anemia, elevated liver enzymes and low platelet count. Eclampsia This is when tonic-clonic seizures appear in a pregnant woman with high blood pressure and proteinuria. Pre-eclampsia and eclampsia are sometimes treated as components of a common syndrome.[5] ## Treatment[edit] There is no specific treatment, but is monitored closely to rapidly identify pre-eclampsia and its life-threatening complications (HELLP syndrome and eclampsia). Drug treatment options are limited, as many antihypertensives may negatively affect the fetus. Methyldopa, hydralazine, and labetalol are most commonly used for severe pregnancy hypertension.[6] The fetus is at increased risk for a variety of life-threatening conditions, including pulmonary hypoplasia (immature lungs). If the dangerous complications appear after the fetus has reached a point of viability, even though still immature, then an early delivery may be warranted to save the lives of both mother and baby. An appropriate plan for labor and delivery includes selection of a hospital with provisions for advanced life support of newborn babies. ## Evolutionary considerations[edit] ### Humans[edit] Gestational hypertension is one of the most common disorders seen in human pregnancies.[7] Though relatively benign on its own, in roughly half of the cases of gestational hypertension the disorder progresses into pre-eclampsia, a dangerous condition that can prove fatal to expectant mothers.[8] However, gestational hypertension is a condition that is fairly rare to see in other animals. For years, it has been the belief of the scientific community that gestational hypertension and pre-eclampsia were relatively unique to humans, although there has been some recent evidence that other primates can also suffer from similar conditions, albeit due to different underlying mechanisms.[7] The underlying cause of gestational hypertension in humans is commonly believed to be an improperly implanted placenta. Humans have evolved to have a very invasive placenta to facilitate better oxygen transfer from the mother to the fetus, to support the growth of its large brain.[9] ### Origins of the placenta[edit] Placental circulation The origins of gestational hypertension may lie with the development of humans' hemochorial placenta. A hemochorial placenta optimizes the amount of oxygen and nutrients that can be absorbed into the fetal blood supply, while at the same time ensuring rapid diffusion of wastes away from the fetus. This hemochorial placenta differs from lower primates' epitheliochorial placentae in the way that it allows the fetal tissues to interact directly with the mother's blood. The hemochorial placenta thereby promotes more rapid diffusion to and from the fetal blood supply.[10] In animals with epitheliochorial placentae such as horses and pigs, the greatest resistance to maternal blood flow in the vascular system was found within the placenta. However, in animals with hemochorial placental structures such as rodents and primates, the vascular resistance in the placenta was low, leading scientists to the conclusion that the greatest resistance to maternal blood flow is found elsewhere in the maternal vascular system.[11] The high vascular resistance outside of the placenta leads to higher maternal blood pressure throughout the body. The fetal cells that implant into the uterine wall are known as the trophoblast. The hemochorial placenta bathes the fetal trophoblast in maternal blood by forming lacunae, or lakes, of the mother's blood that surround fetal tissue. The lacunae are filled by the spiral arteries, which means that the mother's blood pressure is the driving force behind the introduction of new blood, which contains both oxygen and food for the fetus, to the system.[12] It is thought that humans need the increased diffusion provided by the hemochorial placenta in order to grow the large brains compared to their body size that distinguish them from other primates.[13] ### Incorrect placental implantation[edit] It is thought that "failings" in normal hemochorial placental structure lead to pre-eclampsia and gestational hypertension.[14] The human placenta implants "earlier, deeper, and more extensively" into the uterine wall, which can potentially lead to many problems that are found in human pregnancies, but not as much in other animals. Miscarriage and pre-eclampsia are both very rare in other species, but are two of the most common pregnancy-related diseases in humans.[15] The genetic roots of gestational hypertension and pre-eclampsia are certain, as women with a family history of the condition are three times more likely to suffer from it when they are pregnant.[16] One of the potential causes of gestational hypertension and pre-eclampsia is when the trophoblast does not invade far enough into the uterine lining.[17] When the fetus's trophoblast does not fully extend into the uterine wall, the spiral arteries do not become fully converted into low-resistance channels.[15] It has been found that this incomplete conversion of spiral arteries increases the resistance to uterine blood flow during pregnancy, and that this occurrence was associated with gestational hypertension.[18] One potential cause of this incomplete breach of the spiral arteries that leads to gestational hypertension is a mistaken immune response by the maternal tissue, reaction to the alien fetal tissue.[19] Therefore, it is clear that the complication of gestational hypertension has roots in the early implantation of the fetus in the uterine wall, an implantation technique that is unique to humans. The highly invasive placenta that is found in humans is thought to be linked to humans' high circulating levels of the hormones CG and hCG. It has been shown that the higher the levels of these hormones, the deeper the trophoblast's invasion into the uterine wall. Instances of gestational hypertension and pre-eclampsia have been shown to occur when the invasion of the uterine wall is not deep enough, because of lower CG and hCG levels in the mother.[20] ### Evolutionary tradeoff[edit] Despite these risks for gestational hypertension, the hemochorial placenta has been favored because of its advantages in the way that it aids in diffusion from mother to fetus later in pregnancy. The bipedal posture that has allowed humans to walk upright has also led to a reduced cardiac output, and it has been suggested that this is what necessitated humans' aggressive early placental structures.[21] Increased maternal blood pressure can attempt to make up for lower cardiac output, ensuring that the fetus's growing brain receives enough oxygen and nutrients.[20] The benefits of being able to walk upright and run on land have outweighed the disadvantages that come from bipedalism, including the placental diseases of pregnancy, such as gestational hypertension. Similarly, the advantages of having a large brain size have outweighed the deleterious effects of having a placenta that does not always convert the spiral arteries effectively, leaving humans vulnerable to contracting gestational hypertension. It is speculated that this was not the case with Neanderthals, and that they died out because their cranial capacity increased too much, and their placentae were not equipped to handle the fetal brain development, leading to widespread pre-eclampsia and maternal and fetal death.[22] Gestational hypertension in the early stages of pregnancy (trimester 1) has been shown to improve the health of the child both in its first year of life, and its later life.[23] However, when the disease develops later in the pregnancy (subsequent trimesters), or turns into pre-eclampsia, there begin to be detrimental health effects for the fetus, including low birth-weight.[8] It has been proposed that fetal genes designed to increase the mother's blood pressure are so beneficial that they outweigh the potential negative effects that can come from pre-eclampsia.[23] It has also been suggested that gestational hypertension and pre-eclampsia have remained active traits due to the cultural capacity of humans, and the tendency for midwives or helpers to aid in delivering babies.[24] ### Relevance of evolutionary history[edit] It is the goal of evolutionary medicine to find treatments for diseases that are informed by the evolutionary history of a disease. It has been suggested that gestational hypertension is linked to insulin resistance during pregnancy.[25] Both the increase in blood sugar that can lead to gestational diabetes and the increase in blood pressure that can lead to gestational hypertension are mechanisms that mean to optimize the amount of nutrients that can be passed from maternal tissue to fetal tissue. It has been suggested that techniques used to combat insulin insensitivity might also prove beneficial to those suffering from gestational hypertension.[25] Measures to avoid insulin resistance include avoiding obesity before pregnancy, minimizing weight gain during pregnancy, eating foods with low glycemic indices, and exercising.[25] ## References[edit] 1. ^ a b "40". Williams obstetrics (24th ed.). McGraw-Hill Professional. 2014. ISBN 9780071798938. 2. ^ a b c d "Gestational Hypertension". Stanford Children's Health. Retrieved 2017-11-30. 3. ^ Garg AX, Nevis IF, McArthur E, Sontrop JM, Koval JJ, Lam NN, Hildebrand AM, Reese PP, Storsley L, Gill JS, Segev DL, Habbous S, Bugeja A, Knoll GA, Dipchand C, Monroy-Cuadros M, Lentine KL (January 2015). "Gestational hypertension and preeclampsia in living kidney donors". N. Engl. J. Med. 372 (2): 124–33. doi:10.1056/NEJMoa1408932. PMC 4362716. PMID 25397608. 4. ^ Lo, JO; Mission, JF; Caughey, AB (April 2013). "Hypertensive disease of pregnancy and maternal mortality". Current Opinion in Obstetrics and Gynecology. 25 (2): 124–32. doi:10.1097/gco.0b013e32835e0ef5. PMID 23403779. S2CID 246228. 5. ^ "preeclampsia/eclampsia" at Dorland's Medical Dictionary 6. ^ Brown CM, Garovic VD (March 2014). "Drug Treatment of Hypertension in Pregnancy". Drugs. 74 (3): 283–296. doi:10.1007/s40265-014-0187-7. PMC 4558097. PMID 24554373. Retrieved 3 September 2020. 7. ^ a b Abrams ET, Rutherford JN (2011). "Framing postpartum hemorrhage as a consequence of human placental biology: an evolutionary and comparative perspective". Am Anthropol. 113 (3): 417–30. doi:10.1111/j.1548-1433.2011.01351.x. PMC 3168987. PMID 21909154. 8. ^ a b Barton JR, O'brien JM, Bergauer NK, Jacques DL, Sibai BM (April 2001). "Mild gestational hypertension remote from term: progression and outcome". Am. J. Obstet. Gynecol. 184 (5): 979–83. doi:10.1067/mob.2001.112905. PMID 11303208. 9. ^ Rosenberg KR, Trevathan WR (December 2007). "An anthropological perspective on the evolutionary context of preeclampsia in humans". J. Reprod. Immunol. 76 (1–2): 91–7. doi:10.1016/j.jri.2007.03.011. PMID 17499857. 10. ^ Campbell, Bernard Grant. "Reproduction and the Placenta." Human Evolution: An Introduction to Man's Adaptations. New York: Aldine De Gruyter, 1998. 317-20. 11. ^ Moll W, Künzel W (January 1973). "The blood pressure in arteries entering the placentae of guinea pigs, rats, rabbits, and sheep". Pflügers Arch. 338 (2): 125–31. doi:10.1007/bf00592748. PMID 4734441. S2CID 24904753. 12. ^ Ahokas RA, McKinney ET (2009). "Development and Physiology of the Placenta and Membranes". The Global Library of Women's Medicine. doi:10.3843/GLOWM.10101. ISSN 1756-2228. 13. ^ Martin RD (August 2003). "Human reproduction: a comparative background for medical hypotheses". J. Reprod. Immunol. 59 (2): 111–35. doi:10.1016/s0165-0378(03)00042-1. PMID 12896817. 14. ^ Cross JC (2003). "The Genetics of Pre-eclampsia: A Feto-placental or Maternal Problem?". Clinical Genetics. 64 (2): 96–103. doi:10.1034/j.1399-0004.2003.00127.x. PMID 12859402. S2CID 23691148. 15. ^ a b Jauniaux E, Poston L, Burton GJ (2006). "Placental-related diseases of pregnancy: Involvement of oxidative stress and implications in human evolution". Hum. Reprod. Update. 12 (6): 747–55. doi:10.1093/humupd/dml016. PMC 1876942. PMID 16682385. 16. ^ Duckitt K, Harrington D (March 2005). "Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies". BMJ. 330 (7491): 565. doi:10.1136/bmj.38380.674340.E0. PMC 554027. PMID 15743856. 17. ^ Norwitz ER (October 2006). "Defective implantation and placentation: laying the blueprint for pregnancy complications". Reprod. Biomed. Online. 13 (4): 591–9. doi:10.1016/s1472-6483(10)60649-9. PMID 17007686. 18. ^ Olofsson P, Laurini RN, Marsál K (May 1993). "A high uterine artery pulsatility index reflects a defective development of placental bed spiral arteries in pregnancies complicated by hypertension and fetal growth retardation". Eur. J. Obstet. Gynecol. Reprod. Biol. 49 (3): 161–8. doi:10.1016/0028-2243(93)90265-e. PMID 8405630. 19. ^ Robertson WB, Brosens I, Dixon G (1976). "Maternal uterine vascular lesions in the hypertensive complications of pregnancy". Perspect Nephrol Hypertens. 5: 115–27. PMID 1005030. 20. ^ a b Cole LA (November 2009). "hCG and hyperglycosylated hCG in the establishment and evolution of hemochorial placentation". J. Reprod. Immunol. 82 (2): 112–18. doi:10.1016/j.jri.2009.04.007. PMID 19560212. 21. ^ Rockwell LC, Vargas E, Moore LG (2003). "Human physiological adaptation to pregnancy: inter- and intraspecific perspectives". Am. J. Hum. Biol. 15 (3): 330–41. doi:10.1002/ajhb.10151. PMID 12704709. S2CID 19806255. 22. ^ Chaline J (August 2003). "Increased cranial capacity in hominid evolution and preeclampsia". J. Reprod. Immunol. 59 (2): 137–52. doi:10.1016/s0165-0378(03)00043-3. PMID 12896818. 23. ^ a b Hollegaard B, Byars SG, Lykke J, Boomsma JJ (2013). "Parent-offspring conflict and the persistence of pregnancy-induced hypertension in modern humans". PLOS ONE. 8 (2): e56821. Bibcode:2013PLoSO...856821H. doi:10.1371/journal.pone.0056821. PMC 3581540. PMID 23451092. 24. ^ Rosenberg Karen R.; Trevathan Wenda R. (2007). "An Anthropological Perspective on the Evolutionary Context of Preeclampsia in Humans". Journal of Reproductive Immunology. 76 (1–2): 91–97. doi:10.1016/j.jri.2007.03.011. PMID 17499857. 25. ^ a b c Solomon CG, Seely EW (February 2001). "Brief review: hypertension in pregnancy : a manifestation of the insulin resistance syndrome?". Hypertension. 37 (2): 232–9. doi:10.1161/01.hyp.37.2.232. PMID 11230277. ## External links[edit] Classification D * ICD-10: O13-O14 * ICD-9-CM: 642 * MeSH: D046110 * DiseasesDB: 5208 External resources * MedlinePlus: 000898 * eMedicine: med/3250 * v * t * e Pathology of pregnancy, childbirth and the puerperium Pregnancy Pregnancy with abortive outcome * Abortion * Ectopic pregnancy * Abdominal * Cervical * Interstitial * Ovarian * Heterotopic * Embryo loss * Fetal resorption * Molar pregnancy * Miscarriage * Stillbirth Oedema, proteinuria and hypertensive disorders * Gestational hypertension * Pre-eclampsia * HELLP syndrome * Eclampsia Other, predominantly related to pregnancy Digestive system * Acute fatty liver of pregnancy * Gestational diabetes * Hepatitis E * Hyperemesis gravidarum * Intrahepatic cholestasis of pregnancy Integumentary system / dermatoses of pregnancy * Gestational pemphigoid * Impetigo herpetiformis * Intrahepatic cholestasis of pregnancy * Linea nigra * Prurigo gestationis * Pruritic folliculitis of pregnancy * Pruritic urticarial papules and plaques of pregnancy (PUPPP) * Striae gravidarum Nervous system * Chorea gravidarum Blood * Gestational thrombocytopenia * Pregnancy-induced hypercoagulability Maternal care related to the fetus and amniotic cavity * amniotic fluid * Oligohydramnios * Polyhydramnios * Braxton Hicks contractions * chorion / amnion * Amniotic band syndrome * Chorioamnionitis * Chorionic hematoma * Monoamniotic twins * Premature rupture of membranes * Obstetrical bleeding * Antepartum * placenta * Circumvallate placenta * Monochorionic twins * Placenta accreta * Placenta praevia * Placental abruption * Twin-to-twin transfusion syndrome Labor * Amniotic fluid embolism * Cephalopelvic disproportion * Dystocia * Shoulder dystocia * Fetal distress * Locked twins * Nuchal cord * Obstetrical bleeding * Postpartum * Pain management during childbirth * placenta * Placenta accreta * Preterm birth * Postmature birth * Umbilical cord prolapse * Uterine inversion * Uterine rupture * Vasa praevia Puerperal * Breastfeeding difficulties * Low milk supply * Cracked nipples * Breast engorgement * Childbirth-related posttraumatic stress disorder * Diastasis symphysis pubis * Postpartum bleeding * Peripartum cardiomyopathy * Postpartum depression * Postpartum psychosis * Postpartum thyroiditis * Puerperal fever * Puerperal mastitis Other * Concomitant conditions * Diabetes mellitus * Systemic lupus erythematosus * Thyroid disorders * Maternal death * Sexual activity during pregnancy * Category [1] 1. ^ https://speciality.medicaldialogues.in/pregnancy-hypertension-high-blood-pressure-during-pregnancy-linked-to-heart-failure-and-stroke-later/ [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Gestational hypertension	c0852260	3,923	wikipedia	https://en.wikipedia.org/wiki/Gestational_hypertension	2021-01-18T18:37:37	{"umls": ["C0852260"], "icd-10": ["O13"], "wikidata": ["Q1519482"]}
A number sign (#) is used with this entry because of evidence that Schopf-Schulz-Passarge syndrome (SSPS) is caused by homozygous mutation in the WNT10A gene (606268) on chromosome 2q35. Clinical Features Schopf et al. (1971) described keratosis palmoplantaris with hypodontia, hypotrichosis, and cysts of the eyelids in sisters whose parents were first cousins. The deciduous teeth were lost early and the permanent dentition in 1 patient consisted only of 2 incisors and a molar. Palmoplantar keratosis and fragility of the nails began at about age 12. At age 25, head hair became sparse and body hair was lost completely. Cysts of both upper and lower eyelids were noted at age 60. The cysts were thought to be derived from the glands of Moll. Font et al. (1986) reported a family with 3 affected brothers who showed manifestations fairly similar to those in the family reported by Schopf et al. (1971). However, whereas Schopf et al. (1971) thought that their patients might have Papillon-Lefevre syndrome (245000), Font et al. (1986) concluded that both families had a separate disorder, which is distinguished by the occurrence of apocrine hidrocystomas of the eyelid margins. Monk et al. (1992) described an English family in which a 62-year-old woman and her 58-and 51-year-old brothers had what the authors referred to as the Schopf-Schulz-Passarge syndrome. They found previous reports of only 8 cases, including those of Burket et al. (1984), Nordin et al. (1988), and Perret (1989). The woman reported by Monk et al. (1992) had thickening of the skin of her palms and soles for 15 years and had had a hypernephroma and a basal cell carcinoma of the skin. Abnormality of deciduous teeth had been noted on school examination and no secondary teeth had ever erupted. She had scanty scalp hair and the fingernails were hypoplastic. The eyelid margins of both eyes showed numerous cysts 1-2 mm in diameter, some clear and others showing a milky opacity. The brothers had essentially identical findings. One of the sibs had an unaffected son. Stevens et al. (1996) provided a comprehensive classification of the primary palmoplantar keratodermas. Where more than a single ectodermal structure was involved, as in this condition, they coined the term 'palmoplantar ectodermal dysplasia' to emphasize the generalized nature of the disorder. They further identified a total of 19 subtypes, the Schopf-Schultz-Passarge syndrome being type XIX. Gorlin (1997) concluded that eccrine tumors with ectodermal dysplasia as described by Nordin et al. (1988) is in fact Schopf syndrome. Among the 8 children of normal parents, Nordin et al. (1988) observed 2 brothers and a sister with ectodermal dysplasia manifested by hypodontia, onychodystrophy, trichodysplasia, and palmoplantar keratosis. In addition, a diffuse palmoplantar eccrine hyperplasia, as well as tumors and cysts of eccrine origin, was noted. The parents were not known to be consanguineous. All 3 affected sibs, in their 70s or 80s, had children, and 2 of them had grandchildren, all unaffected. Eccrine glands, also known as exocrine glands, include the sweat glands. Excessive sweating of the hands and feet was described. One of the patients had a cauliflower-like tumor on the heel, with secretions that stained the coverings of the heel. In later years the patients developed nodules on the bodies of the upper and lower eyelids. Eyelashes and eyebrows were sparse, but scalp and body hair was described as unremarkable. Craigen et al. (1997) stated that 10 cases of this syndrome had been reported; all were compatible with autosomal recessive inheritance except for the family reported by Kuster and Hammerstein (1992), which exhibited dominant inheritance. They reported a family in which 3 full sibs and 1 half sib, all males, had Schopf-Schultz-Passarge syndrome. The half sibs shared a father. The 4 affected males had a total of 8 sons and 4 daughters, none of whom were affected. Craigen et al. (1997) presented photographs of the eyelid cysts, nail dystrophy, and dry erythematous palm of 1 of the patients. Mallaiah and Dickinson (2001) presented a photo essay of eyelid cysts, plantar hyperkeratosis, dysplastic toenails, and adontia in sibs in their sixth decade who had become symptomatic in their third decade. Histopathology of apocrine hidrocystomas was included. Additionally, the authors commented that simple excision of eyelid cysts was rarely adequate and that en bloc excision of the anterior lamella of the eyelids might be beneficial. Molecular Genetics In a female patient with cysts of the eyelids in addition to hypodontia, hypotrichosis, hyperhidrosis, palmoplantar hyperkeratosis, and dystrophic nails, who was negative for mutation in the ectodysplasin-A gene (EDA; 300451), Bohring et al. (2009) identified homozygosity for a nonsense mutation in the WNT10A gene (606268.0001). They also found homozygous or compound heterozygous WNT10A mutations in 8 patients with odontoonychodermal dysplasia (OODD; 257980) but no eyelid cysts. The proband with SSPS had 2 brothers who were heterozygous for the mutation and exhibited dental anomalies: one had agenesis of both lower central incisors, and the other had anomalies of the upper lateral permanent incisors. The proband was also diagnosed with a porocarcinoma of the left heel. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Bird-like facies Eyes \- Eyelid margin cysts (hidrocystoma) Teeth \- Hypodontia SKIN, NAILS, & HAIR Skin \- Palmoplantar keratoderma \- Eyelid margin cysts (apocrine hidrocystoma) \- Eccrine poroma Nails \- Hypoplastic nails \- Thin, narrow nails \- Longitudinal ridging \- Onycholysis Hair \- Hypotrichosis (scalp) NEOPLASIA \- Basal cell carcinoma \- Squamous cell carcinoma MOLECULAR BASIS \- Caused by mutation in the wingless-type MMTV integration site family, member 10A gene (WNT10A, 606268.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	SCHOPF-SCHULZ-PASSARGE SYNDROME	c1857069	3,924	omim	https://www.omim.org/entry/224750	2019-09-22T16:28:27	{"mesh": ["C565607"], "omim": ["224750"], "orphanet": ["50944"], "synonyms": ["Alternative titles", "KERATOSIS PALMOPLANTARIS WITH CYSTIC EYELIDS, HYPODONTIA, AND HYPOTRICHOSIS", "ECCRINE TUMORS WITH ECTODERMAL DYSPLASIA"]}
Transient neonatal pustular melanosis Other namesTransient neonatal pustulosis[1] and lentigines neonatorum[2] Transient neonatal pustular melanosis SpecialtyDermatology Transient neonatal pustular melanosis (TNPM), also known as pustular melanosis, is a transient rash common in newborns. It is vesiculopustular and made up of 1-3 mm fluid-filled lesions that rupture, leaving behind a collarette of scale and a brown macule.[3] This rash occurs only in the newborn stage, usually appearing a few days after birth[2], but is sometimes already present at birth[3]. The rash usually fades over three to four weeks but may linger for up to three months after birth.[3] It can occur anywhere on the body, including the palms and soles.[1][2][3] The cause of TNPM is unknown. No treatment is needed except for parental reassurance. ## Contents * 1 Causes * 2 Histopathology * 3 Diagnosis * 4 Treatment * 5 Epidemiology * 6 See also * 7 References ## Causes[edit] The cause of TNPM is unknown but it is a common rash in newborns.[3] ## Histopathology[edit] Gram, Wright, or Giemsa staining of the pustular contents will show polymorphic neutrophils and occasional eosinophils.[2][3] On histopathology, the pigmented macules will show basal and supra-basal increase in pigmentation without any pigmentary incontinence.[3] Bacterial culture will be negative.[4] It has been suggested that TNPM is merely a precocious form of erythema toxicum neonatorum based on the similar histopathology.[4] ## Diagnosis[edit] Transient neonatal pustular melanosis is diagnosed clinically, based on appearance alone, with no need for special testing. Proper identification is important to distinguish it from other serious, infectious neonatal diseases[3] and to help avoid unnecessary diagnostic testing and treatments. ## Treatment[edit] No treatment is needed except for parental reassurance. The rash spontaneously resolves, usually in three to four weeks, but may linger for up to three months after birth.[3] ## Epidemiology[edit] Transient neonatal pustular melanosis occurs in as much as 15% of black newborns.[3] but in less than 1% of white newborns. [2] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. 2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 476. ISBN 978-1-4160-2999-1. 1\. O'Connor NR, McLaughlin, MR, Ham P (2008). “Newborn Skin: Part I. Common Newborn Rashes”. American Family Physician. 77 (1): 47-52. 2\. Patrizi A, Neri I, Virid A, Gurioli C.(2016). “Frequent newborn skin diseases”. Clinical Dermatology. 4 (3-4): 82-86. doi: 10.11138/cderm/2016.4.3.082. 3\. Ghosh S. (2015). “Neonatal Pustular Dermatosis: An Overview”. Indian Journal of Dermatology. 60 (2): 211. doi: 10.4103/0019-5154.152558 4\. Ferrándiz C, Coroleu W, Ribera M, Lorenzo JC, Natal A (1992). “Sterile transient neonatal pustulosis is a precocious form of erythema toxicum neonatorum”. Dermatology. 185:18–22. 5\. Mebazaa A, Khaddar-Kort R, Cherif M, Mokni S, Haouet A, Osman B (2011). “Transient pustular eruption in neonates”. Archives de Pediatrie. 18 (3) 291-293. 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	Transient neonatal pustular melanosis	c0406782	3,925	wikipedia	https://en.wikipedia.org/wiki/Transient_neonatal_pustular_melanosis	2021-01-18T18:52:01	{"umls": ["C0406782"], "icd-10": ["P83.8"], "wikidata": ["Q6009373"]}
Esca Esca symptoms on leaves Causal agentsPhaeoacremonium aleophilum, Phaeomoniella chlamydospora HostsVitis vinifera EPPO CodeTOGNMI, PHMOCH Esca is a grape disease of mature grapevines. It is a type of grapevine trunk disease. The fungi Phaeoacremonium aleophilum, Phaeomoniella chlamydospora[1] and Fomitiporia mediterranea[2] are associated with the disease. ## See also[edit] * List of grape diseases ## References[edit] 1. ^ Martín, M. T.; Cobos, R; Martín, L; López-Enríquez, L (2012). "Real-Time PCR Detection of Phaeomoniella chlamydospora and Phaeoacremonium aleophilum". Applied and Environmental Microbiology. 78 (11): 3985–3991. doi:10.1128/AEM.07360-11. PMC 3346403. PMID 22447605. 2. ^ Fischer, Michael (2002). "A new wood-decaying basidiomycete species associated with esca of grapevine: Fomitiporia mediterranea (Hymenochaetales)". Mycological Progress. 1 (3): 315–324. doi:10.1007/s11557-006-0029-4. S2CID 41692047. ## External links[edit] [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Esca (grape disease)	None	3,926	wikipedia	https://en.wikipedia.org/wiki/Esca_(grape_disease)	2021-01-18T18:52:49	{"wikidata": ["Q284145"]}
On the basis of a genomic search for linkage, Verge et al. (1998) concluded that a locus contributing to type I diabetes in a large Bedouin Arab family was located on 10q25. The family contained 19 affected relatives all of whom carried 1 or 2 high-risk HLA-DR3 haplotypes that were rarely found in other family members. One chromosome 10 haplotype, the B haplotype, was transmitted from a heterozygous parent to 13 of 13 offspring compared to 10 of 23 unaffected sibs. Recombination events occurring on this haplotype placed the susceptibility locus in an 8-cM interval between D10S1750 and D10S1773. Two adjacent markers, D10S592 and D10S554, showed evidence of linkage disequilibrium with the disease locus. These 2 markers and the closest flanking markers were contained in a 1,240-kb YAC, a region small enough to make positional cloning feasible. Six of 14 or more IDDM loci previously reported in studies of Caucasian affected sib pairs (Luo et al., 1996) met the suggested criteria for confirmed linkage (Lander and Kruglyak, 1995), but none of these loci corresponded to the locus at 10q25. These 6 loci were IDDM1 (222100), linked to HLA, IDDM2 (125852), linked to the INS gene (176730), IDDM4 (600319) at 11q13, IDDM5 (600320) at 6q25, IDDM8 (600883) at 6q27, and IDDM12 (601388) at 2q33 where linkage disequilibrium with the CTLA4 locus (123890) has been found. Verge et al. (1998) commented that Bedouin Arabs living in Israel showed a remarkably low overall frequency of diabetes compared with Israeli Jews, yet Bedouin Arab tribes with multiple affected members are not uncommon. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: 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 MELLITUS, INSULIN-DEPENDENT, 17	c1864068	3,927	omim	https://www.omim.org/entry/603266	2019-09-22T16:13:08	{"mesh": ["C566395"], "omim": ["603266"], "synonyms": ["Alternative titles", "INSULIN-DEPENDENT DIABETES MELLITUS 17"]}
Xanthoma disseminatum Other namesDisseminated xanthosiderohistiocytosis[1] and Montgomery syndrome[2] SpecialtyEndocrinology Xanthoma disseminatum is a rare cutaneous condition that preferentially affects males in childhood, characterized by the insidious onset of small, yellow-red to brown papules and nodules that are discrete and disseminated.[2]:717 It is a histiocytosis syndrome.[3] ## See also[edit] * Non-X histiocytosis * List of cutaneous conditions ## References[edit] 1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 2. ^ a b James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6. 3. ^ Alexander AS, Turner R, Uniate L, Pearcy RG (February 2005). "Xanthoma disseminatum: a case report and literature review". Br J Radiol. 78 (926): 153–7. doi:10.1259/bjr/27500851. PMID 15681329. ## External links[edit] Classification D * ICD-10: E78.2 (ILDS E78.240) * 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 * t * e Histiocytosis WHO-I/Langerhans cell histiocytosis/ X-type histiocytosis * Letterer–Siwe disease * Hand–Schüller–Christian disease * Eosinophilic granuloma * Congenital self-healing reticulohistiocytosis WHO-II/non-Langerhans cell histiocytosis/ Non-X histiocytosis * Juvenile xanthogranuloma * Hemophagocytic lymphohistiocytosis * Erdheim-Chester disease * Niemann–Pick disease * Sea-blue histiocyte * Benign cephalic histiocytosis * Generalized eruptive histiocytoma * Xanthoma disseminatum * Progressive nodular histiocytosis * Papular xanthoma * Hereditary progressive mucinous histiocytosis * Reticulohistiocytosis (Multicentric reticulohistiocytosis, Reticulohistiocytoma) * Indeterminate cell histiocytosis WHO-III/malignant histiocytosis * Histiocytic sarcoma * Langerhans cell sarcoma * Interdigitating dendritic cell sarcoma * Follicular dendritic cell sarcoma Ungrouped * Rosai–Dorfman disease 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	Xanthoma disseminatum	c0043322	3,928	wikipedia	https://en.wikipedia.org/wiki/Xanthoma_disseminatum	2021-01-18T18:33:33	{"gard": ["13186"], "mesh": ["D015616"], "umls": ["C0043322"], "icd-10": ["E78.2"], "orphanet": ["158003"], "wikidata": ["Q8043038"]}
Type of reading disorder Surface dyslexia is a type of dyslexia, or reading disorder.[1][2] According to Marshall & Newcombe's (1973) and McCarthy & Warrington's study (1990), patients with this kind of disorder cannot recognize a word as a whole due to the damage of the left parietal or temporal lobe. Individuals with surface dyslexia are unable to recognize a word as a whole word and retrieve its pronunciation from memory. Rather, individuals with surface dyslexia rely on pronunciation rules. Thus, patients with this particular type of reading disorder read non-words fluently, like "yatchet", but struggle with words that defy pronunciation rules (i.e. exception words). For example, a patient with surface dyslexia can correctly read regular words like "mint", but will err when presented a word that disobeys typical pronunciation rules, like "pint". Often, semantic knowledge is preserved in individuals with surface dyslexia.[3][4] ## Contents * 1 The dual route theory of reading * 2 Treatment * 3 See also * 4 References ## The dual route theory of reading[edit] Main article: Dual-route hypothesis to reading aloud The dual route theory of reading proposes that skilled readers utilize two mechanisms when converting written language to spoken language: the direct, lexical pathway and the indirect, non-lexical pathway. According to the dual route theory of reading, in individuals with surface dyslexia, the indirect (non-lexical) pathway is preserved. However, the direct (lexical) pathway of reading is not. The indirect pathway of reading allows individuals with surface dyslexia to read regular words that follow a letter-sound or grapheme-to-phoneme conversion. The absence of an intact direct pathway of reading leads individuals with surface dyslexia to incorrectly identify and pronounce irregular words.[3][4] ## Treatment[edit] Some studies[which?] have demonstrated improvements in reading and spelling performance of individual children with surface dyslexia. Many of the interventions that exist are based on the dual route model of reading and utilize a targeted approach based on the individual assessment results. Case studies conducted by Law and Cupples (2015) recommend first identifying specific oral reading difficulties experienced by the individual with surface dyslexia and based on the reading patterns identified designing a theoretically motivated and targeted treatment program. One of the interventions involved targeting visual-orthographic processing by increasing the efficiency by which surface dyslexics identified nonwords. The second intervention involved training in the identification and decoding of common letter patterns in irregular words.[5] ## See also[edit] * Aphasia * Agnosia ## References[edit] 1. ^ Carlson, Neil (2010). Psychology the Science of Behaviour [4th Canadian ed.]. Toronto, On. Canada: Pearson Canada Inc. pp. 310. ISBN 978-0-205-64524-4. 2. ^ Cherney LR (2004). "Aphasia, alexia, and oral reading". Top Stroke Rehabil. 11 (1): 22–36. doi:10.1310/VUPX-WDX7-J1EU-00TB. PMID 14872397. 3. ^ a b Playfoot, D (2014). "Naming acronyms: The influence of reading context in skilled reading and surface dyslexia". Aphasiology. 4. ^ a b Wang, H.C. (2015). "Orthographic learning in developmental surface and phonological dyslexia". Cognitive Neuropsychology. 32 (2): 58–79. doi:10.1080/02643294.2014.1003536. PMID 25639641. 5. ^ Law, Caroline; Cupples, Linda (18 August 2015). "Thinking outside the boxes: Using current reading models to assess and treat developmental surface dyslexia". Neuropsychological Rehabilitation. 27 (2): 149–195. doi:10.1080/09602011.2015.1064453. PMID 26282550. * v * t * e Dyslexia and related specific developmental disorders Conditions Speech, language, and communication * Expressive language disorder * Infantile speech * Landau–Kleffner syndrome * Language disorder * Lisp * Mixed receptive-expressive language disorder * Specific language impairment * Speech and language impairment * Speech disorder * Speech error * Speech sound disorder * Stuttering * Tip of the tongue Learning disability * Dyslexia * Dyscalculia * Dysgraphia * Disorder of written expression Motor * Developmental coordination disorder * Developmental verbal dyspraxia Sensory * Auditory processing disorder * Sensory processing disorder Related topics * Dyslexia research * Irlen filters * Learning Ally * Learning problems in childhood cancer * Literacy * Management of dyslexia * Multisensory integration * Neuropsychology * Reading acquisition * Spelling * Writing system Lists * Dyslexia in fiction * Languages by Writing System * People with dyslexia * v * t * e Psychology * History * Philosophy * Portal * Psychologist Basic psychology * Abnormal * Affective science * Affective neuroscience * Behavioral genetics * Behavioral neuroscience * Behaviorism * Cognitive/Cognitivism * Cognitive neuroscience * Social * Comparative * Cross-cultural * Cultural * Developmental * Differential * Ecological * Evolutionary * Experimental * Gestalt * Intelligence * Mathematical * Moral * Neuropsychology * Perception * Personality * Positive * Psycholinguistics * Psychophysiology * Quantitative * Social * Theoretical Applied psychology * Anomalistic * Applied behavior analysis * Assessment * Clinical * Coaching * Community * Consumer * Counseling * Critical * Educational * Ergonomics * Feminist * Forensic * Health * Industrial and organizational * Legal * Media * Medical * Military * Music * Occupational health * Pastoral * Political * Psychometrics * Psychotherapy * Religion * School * Sport and exercise * Suicidology * Systems * Traffic Methodologies * Animal testing * Archival research * Behavior epigenetics * Case study * Content analysis * Experiments * Human subject research * Interviews * Neuroimaging * Observation * Psychophysics * Qualitative research * Quantitative research * Self-report inventory * Statistical surveys Psychologists * Wilhelm Wundt (1832–1920) * William James (1842–1910) * Ivan Pavlov (1849–1936) * Sigmund Freud (1856–1939) * Edward Thorndike (1874–1949) * Carl Jung (1875–1961) * John B. Watson (1878–1958) * Clark L. Hull (1884–1952) * Kurt Lewin (1890–1947) * Jean Piaget (1896–1980) * Gordon Allport (1897–1967) * J. P. Guilford (1897–1987) * Carl Rogers (1902–1987) * Erik Erikson (1902–1994) * B. F. Skinner (1904–1990) * Donald O. Hebb (1904–1985) * Ernest Hilgard (1904–2001) * Harry Harlow (1905–1981) * Raymond Cattell (1905–1998) * Abraham Maslow (1908–1970) * Neal E. Miller (1909–2002) * Jerome Bruner (1915–2016) * Donald T. Campbell (1916–1996) * Hans Eysenck (1916–1997) * Herbert A. Simon (1916–2001) * David McClelland (1917–1998) * Leon Festinger (1919–1989) * George A. 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LeDoux (b. 1949) * Richard Davidson (b. 1951) * Susan Fiske (b. 1952) * Roy Baumeister (b. 1953) Lists * Counseling topics * Disciplines * Important publications * Organizations * Outline * Psychologists * Psychotherapies * Research methods * Schools of thought * Timeline * Topics * Wiktionary definition * Wiktionary category * Wikisource * Wikimedia Commons * Wikiquote * Wikinews * Wikibooks [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Surface dyslexia	c0454594	3,929	wikipedia	https://en.wikipedia.org/wiki/Surface_dyslexia	2021-01-18T18:41:14	{"wikidata": ["Q2868239"]}
Normolipoproteinemic xanthomatosis SpecialtyDermatology Normolipoproteinemic xanthomatosis is a cutaneous condition characterized by a xanthoma in the presence of normal cholesterol and lipoprotein levels.[1]:535 ## See also[edit] * Cerebrotendinous xanthomatosis * Verruciform xanthoma * 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	Normolipoproteinemic xanthomatosis	None	3,930	wikipedia	https://en.wikipedia.org/wiki/Normolipoproteinemic_xanthomatosis	2021-01-18T19:07:00	{"wikidata": ["Q7053146"]}
Endocrine disease Thyroid storm Other namesThyrotoxic crisis SpecialtyEndocrinology Thyroid storm is a rare but severe and potentially life-threatening complication of hyperthyroidism (overactivity of the thyroid gland). It is characterized by a high fever (temperatures often above 40 °C/104 °F), fast and often irregular heart beat, elevated blood pressure, vomiting, diarrhea, and agitation. Hypertension with a wide pulse pressure occurs in early to mid crisis, with hypotension accompanying shock occurring in the late stage.[1] Heart failure and heart attack may occur. Death may occur despite treatment.[2] Most episodes occur either in those with known hyperthyroidism whose treatment has been stopped or become ineffective, or in those with untreated mild hyperthyroidism who have developed an intercurrent illness (such as an infection).[2] The primary treatment of thyroid storm is with inorganic iodine and antithyroid drugs (propylthiouracil or methimazole) to reduce synthesis and release of thyroid hormone. Temperature control and intravenous fluids are also mainstays of management. Beta blockers are often used to reduce the effects of thyroid hormone.[3] Patients often require admission to the intensive care unit.[4] ## Contents * 1 Signs and symptoms * 2 Causes of thyroid storm * 3 Pathophysiology * 3.1 Increases in free thyroid hormone * 3.2 Decrease in thyroid hormone binding protein * 3.3 Increased sensitivity to thyroid hormone * 3.4 Sympathetic activation * 3.5 Thyroid storm as allostatic failure * 4 Diagnosis * 4.1 Laboratory findings * 5 Management * 6 See also * 7 References * 8 External links ## Signs and symptoms[edit] Thyroid storm is characterized by an acute onset of symptoms of hyperthyroidism (fast heart rate, restlessness, agitation) accompanied by other features such as fever (temperatures often above 40 °C/104 °F), hypertension, mental status changes, diarrhea, and vomiting.[5] Individuals can exhibit varying signs of organ dysfunction. Patients may experience liver dysfunction, and jaundice (yellowing of the skin) is considered a poor prognostic sign. Cardiac (heart) symptoms include abnormal heart rhythms, myocardial infarction (heart attack), and congestive heart failure, which may lead to cardiovascular collapse. Mortality can be as high as 20-30%.[6] In some situations, individuals may not experience the classic signs of restlessness and agitation, but instead present with apathetic signs of weakness and confusion.[5] ## Causes of thyroid storm[edit] The transition from hyperthyroidism to thyroid storm is typically triggered by a non-thyroidal insult including, but not limited to fever, sepsis, dehydration, myocardial infarction, and psychiatric diseases.[vague][7][8] Individuals are at higher risk of thyroid storm if their hyperthyroidism is incompletely treated or if their anti-thyroid drugs are discontinued. Many of these individuals have underlying primary causes of hyperthyroidism (Graves disease, toxic multi-nodular goiter, solitary toxic adenoma). However, thyroid storm can occur in individuals with unrecognized thyrotoxicosis experiencing non-thyroid surgery, labor, infection, or exposure to certain medications and radiocontrast dyes.[citation needed] Precipitating factors for thyroid storm[5][9] Severe infection Diabetic ketoacidosis Hypoglycemia Thyroid surgery Non-thyroid surgery Parturition Struma ovarii Molar pregnancy Trauma (i.e. hip fracture) Burns Myocardial infarction Pulmonary embolism Stroke Heart failure Radioactive iodine treatment Medication side effect (anesthetics, salicylate, pseudoephedrine, amiodarone) Exposure to iodinated contrast Withdrawal of antithyroid treatment Emotional stress Intense exercise ## Pathophysiology[edit] The precise mechanism for the development of thyroid storm is poorly understood. In the human body, thyroid hormone may be free (biologically active T3/T4) or bound to thyroid binding hormone (biologically inactive) to be transported. The release of thyroid hormone is tightly regulated by a feedback system involving the hypothalamus, pituitary gland, and thyroid gland. Hyperthyroidism results from a dysregulation of this system that eventually leads to increases in levels of free T3/T4. The transition from simple hyperthyroidism to the medical emergency of thyroid storm may be triggered by conditions (see Causes) that lead to the following: ### Increases in free thyroid hormone[edit] Individuals with thyroid storm tend to have increased levels of free thyroid hormone, although total thyroid hormone levels may not be much higher than in uncomplicated hyperthyroidism.[9] The rise in the availability of free thyroid hormone may be the result of manipulating the thyroid gland. In the setting of an individual receiving radioactive iodine therapy, free thyroid hormone levels may acutely increase due to the release of hormone from ablated thyroid tissue.[citation needed] ### Decrease in thyroid hormone binding protein[edit] A decrease in thyroid hormone binding protein in the setting of various stressors or medications may also cause a rise in free thyroid hormone.[3] ### Increased sensitivity to thyroid hormone[edit] Along with increases in thyroid hormone availability, it is also suggested that thyroid storm is characterized by the body's heightened sensitivity to thyroid hormone, which may be related to sympathetic activation (see below).[9] ### Sympathetic activation[edit] Sympathetic nervous system activation during times of stress may also play a significant role in thyroid storm.[3] Sympathetic activation increases production of thyroid hormone by the thyroid gland. In the setting of elevated thyroid hormone, the density of thyroid hormone receptors (esp. beta-receptors) also increases, which enhances the response to catecholamines. This is likely responsible for several of the cardiovascular symptoms (increased cardiac output, heart rate, stroke volume) seen in thyroid storm.[citation needed][10] ### Thyroid storm as allostatic failure[edit] According to newer theories, thyroid storm results from allostatic failure in a situation where thyrotoxicosis hampers the development of non-thyroidal illness syndrome,[11] which would help to save energy in critical illness and other situations of high metabolic demand.[8] Usually, in critical illness (e.g. sepsis, myocardial infarction and other causes of shock) thyroid function is tuned down to result in low-T3 syndrome and, occasionally, also low TSH concentrations, low-T4 syndrome and impaired plasma protein binding of thyroid hormones. This endocrine pattern is referred to as euthyroid sick syndrome (ESS), non-thyroidal illness syndrome (NTIS) or thyroid allostasis in critical illness, tumours, uraemia and starvation (TACITUS). Although NTIS is associated with significantly worse prognosis, it is also assumed to represent a beneficial adaptation (type 1 allostasis). In cases, where critical illness is accompanied by thyrotoxicosis, this comorbidity prevents the down-regulation of thyroid function. Therefore, the consumption of energy, oxygen and glutathione remains high, which leads to further increased mortality.[11] These new theories imply that thyroid storm results from an interaction of thyrotoxicosis with the specific response of the organism to an oversupply of thyroid hormones.[7] ## Diagnosis[edit] The diagnosis of thyroid storm is based on the presence of signs and symptoms consistent with severe hyperthyroidism.[9] Multiple approaches have been proposed to calculate the probability of thyroid storm based on clinical criteria, however, none have been universally adopted by clinicians. For instance, Burch and Wartofsky published the Burch-Wartofsky point scale (BWPS) in 1993, assigning a numerical value based on the presence of specific signs and symptoms organized within the following categories: temperature, cardiovascular dysfunction (including heart rate and presence of atrial fibrillation or congestive heart failure), central nervous system (CNS) dysfunction, gastrointestinal or liver dysfunction and presence of a precipitating event.[9][12] A Burch-Wartofsky score below 25 is not suggestive of thyroid storm whereas 25 to 45 suggests impending thyroid storm and greater than 45 suggests current thyroid storm.[13] Alternatively, the Japanese Thyroid Association (JTA) criteria, derived from a large cohort of patients with thyroid storm in Japan and published in 2012, provide a qualitative method to determine the probability of thyroid storm. The JTA criteria separate the diagnosis of thyroid storm into definite versus suspected based on the specific combination of signs and symptoms a patient exhibits and require elevated free triiodothyronine (T3) or free thyroxine (T4) for definite thyroid storm.[14] Burch-Wartofsky Point Scale[9] Temperature Score Heart Rate Score Symptoms of Heart Failure Score Presence of Atrial Fibrillation Score Symptoms of CNS Dysfunction Score Gastrointestinal or Liver Dysfunction Score Presence of Precipitating Event Score 99.0 to 99.9 5 90 to 109 5 None 0 Absent 0 None 0 None 0 None 0 100.0 to 100.9 10 110 to 119 10 Mild (i.e. pedal edema) 5 Present 10 Mild (e.g. showing signs of agitation) 10 Moderate (e.g. diarrhea, nausea, vomiting or abdominal pain) 10 Present 10 101.0 to 101.9 15 120 to 129 15 Moderate (i.e. bibasilar rales) 10 Moderate (e.g. delirium, psychosis, lethargy) 20 Severe (i.e. unexplained jaundice) 20 102.0 to 102.9 20 130 to 139 20 Severe (i.e. pulmonary edema) 15 Severe (e.g. seizure or coma) 30 103 to 103.9 25 Greater than or equal to 140 25 Greater than or equal to 104 30 ### Laboratory findings[edit] As with hyperthyroidism, TSH is suppressed. Both free and serum (or total) T3 and T4 are elevated.[5] An elevation in thyroid hormone levels is suggestive of thyroid storm when accompanied by signs of severe hyperthyroidism but is not diagnostic as it may also correlate with uncomplicated hyperthyroidism.[9][12] Moreover, serum T3 may be normal in critically ill patients due to decreased conversion of T4 to T3.[9] Other potential abnormalities include the following:[9][12] * Hyperglycemia likely due to catecholamine-mediated effects on insulin release and metabolism as well as increased glycogenolysis, evolving into hypoglycemia when glycogen stores are depleted * Elevated aspartate aminotransferase (AST), bilirubin and lactate dehydrogenase (LDH) * Hypercalcemia and elevated alkaline phosphatase due to increased bone resorption * Elevated white blood cell count * ## Management[edit] The main strategies for the management of thyroid storm are reducing production and release of thyroid hormone, reducing the effects of thyroid hormone on tissues, replacing fluid losses, and controlling temperature.[3] Thyroid storm requires prompt treatment and hospitalization. Often, admission to the intensive care unit is needed.[15] Iodine Guidelines recommend the administration of inorganic iodide (potassium iodide or Lugol's iodine[4][15]) to reduce the synthesis and release of thyroid hormone. Iodine reduces the synthesis of thyroid hormone via the Wolff-Chaikoff effect.[3] Some guidelines recommend that iodine be administered after antithyroid medications are started, because iodine is also a substrate for the synthesis of thyroid hormone, and may worsen hyperthyroidism if administered without antithyroid medications.[3] Antithyroid Medications Antithyroid drugs (propylthiouracil or methimazole) are used to reduce the synthesis and release of thyroid hormone. Propylthiouracil is preferred over methimazole due to its additional effects on reducing peripheral conversion of T4 to T3,[3] however both are commonly used. Beta Blockers The administration of beta-1-selective beta blockers (e.g. metoprolol) is recommended to reduce the effect of circulating thyroid hormone on end organs.[2][15][4] In addition, propranolol at high doses also reduces peripheral conversion of T4 to T3, which is the more active form of thyroid hormone.[15] Although previously non-selective beta blockers (e.g., propranolol) have been suggested to be beneficial due to their inhibitory effects on peripheral deiodinases, recent research suggests them to be associated with increased mortality.[16] Therefore, cardioselective beta blockers may be favourable.[8] Corticosteroids High levels of thyroid hormone result in a hypermetabolic state, which can result in increased breakdown of cortisol, a hormone produced by the adrenal gland. This results in a state of relative adrenal insufficiency, in which the amount of cortisol is not sufficient.[16] Guidelines recommend that corticosteroids (hydrocortisone and dexamethasone are preferred over prednisolone or methylprednisolone) be administered to all patients with thyroid storm. However, doses should be altered for each individual patient to ensure that the relative adrenal insufficiency is adequately treated while minimizing the risk of side effects.[16] Supportive Measures In high fever, temperature control is achieved with fever reducers such as paracetamol/acetaminophen and external cooling measures (cool blankets, ice packs). Dehydration, which occurs due to fluid loss from sweating, diarrhea, and vomiting, is treated with frequent fluid replacement.[15] In severe cases, mechanical ventilation may be necessary. Any suspected underlying cause is also addressed.[2] ## See also[edit] * Myxedema coma * Euthyroid sick syndrome ## References[edit] 1. ^ "Thyroid Storm Clinical Presentation: History, Physical Examination, Complications". 2. ^ a b c d Klubo-Gwiezdzinska, Joanna; Wartofsky, Leonard (March 2012). "Thyroid emergencies". Medical Clinics of North America. 96 (2): 385–403. doi:10.1016/j.mcna.2012.01.015. PMID 22443982. 3. ^ a b c d e f g Chiha M; Samara S; Kabaker A (March 2015). "Thyroid Storm: An Updated Review". Journal of Intensive Care Medicine. 30 (3): 131–140. doi:10.1177/0885066613498053. PMID 23920160. S2CID 21369274.CS1 maint: uses authors parameter (link) 4. ^ a b c Bahn, RS; Burch, HB; Cooper, DS; Garber, JR; Greenlee, MC; Klein, I; Laurberg, P; McDougall, IR; Montori, VM; Rivkees, SA; Ross, DS; Sosa, JA; Stan, MN; American Thyroid, Association; American Association of Clinical, Endocrinologists (June 2011). "Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists". Thyroid. 21 (6): 593–646. doi:10.1089/thy.2010.0417. PMID 21510801.CS1 maint: uses authors parameter (link) 5. ^ a b c d Gardner DG (2017). "Endocrine Emergencies". In Gardner DG, Shoback D (eds.). Greenspan's Basic and Clinical Endocrinology (10 ed.). New York: McGraw-Hill. 6. ^ Paulson JM, Hollenberg AN (2017). "Thyroid Emergencies". In McKean SC, Ross JJ, Dressler DD, Scheurer DB (eds.). Principles and Practice of Hospital Medicine (2 ed.). New York: McGraw-Hill. ISBN 978-0-07-184313-3. 7. ^ a b Dietrich, JW (September 2012). "Thyreotoxische Krise [Thyroid storm]". Medizinische Klinik, Intensivmedizin und Notfallmedizin. 107 (6): 448–53. doi:10.1007/s00063-012-0113-2. PMID 22878518. S2CID 31285541. 8. ^ a b c Dietrich, J. (15 June 2016). "Thyreotoxische Krise und Myxödemkoma". Der Nuklearmediziner. 39 (2): 124–131. doi:10.1055/s-0042-105786. 9. ^ a b c d e f g h i Chiha, Maguy; Samarasinghe, Shanika; Kabaker, Adam S. (2013-08-05). "Thyroid Storm". Journal of Intensive Care Medicine. 30 (3): 131–140. doi:10.1177/0885066613498053. PMID 23920160. S2CID 21369274. 10. ^ Holt, Elizabeth H.; Peery, Harry E. (28 July 2010). Basic Medical Endocrinology (4th ed.). pp. 52–53. ISBN 9780080920559. 11. ^ a b Chatzitomaris, Apostolos; Hoermann, Rudolf; Midgley, John E.; Hering, Steffen; Urban, Aline; Dietrich, Barbara; Abood, Assjana; Klein, Harald H.; Dietrich, Johannes W. (20 July 2017). "Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming". Frontiers in Endocrinology. 8: 163. doi:10.3389/fendo.2017.00163. PMC 5517413. PMID 28775711. 12. ^ a b c Klubo-Gwiezdzinska, Joanna; Wartofsky, Leonard (March 2012). "Thyroid emergencies". The Medical Clinics of North America. 96 (2): 385–403. doi:10.1016/j.mcna.2012.01.015. ISSN 1557-9859. PMID 22443982. 13. ^ Burch, H. B.; Wartofsky, L. (June 1993). "Life-threatening thyrotoxicosis. Thyroid storm". Endocrinology and Metabolism Clinics of North America. 22 (2): 263–277. doi:10.1016/S0889-8529(18)30165-8. ISSN 0889-8529. PMID 8325286. 14. ^ Akamizu, Takashi; Satoh, Tetsurou; Isozaki, Osamu; Suzuki, Atsushi; Wakino, Shu; Iburi, Tadao; Tsuboi, Kumiko; Monden, Tsuyoshi; Kouki, Tsuyoshi (July 2012). "Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys". Thyroid. 22 (7): 661–679. doi:10.1089/thy.2011.0334. ISSN 1557-9077. PMC 3387770. PMID 22690898. 15. ^ a b c d e Bahn, RS; Burch, HB; Cooper, DS; Garber, JR; Greenlee, MC; Klein, I; Laurberg, P; McDougall, IR; Montori, VM; Rivkees, SA; Ross, DS; Sosa, JA; Stan, MN; American Thyroid, Association; American Association of Clinical, Endocrinologists (June 2011). "Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists". Thyroid. 21 (6): 593–646. doi:10.1089/thy.2010.0417. PMID 21510801.CS1 maint: uses authors parameter (link) 16. ^ a b c Isozaki, O; Satoh, T; Wakino, S; Suzuki, A; Iburi, T; Tsuboi, K; Kanamoto, N; Otani, H; Furukawa, Y; Teramukai, S; Akamizu, T (June 2016). "Treatment and management of thyroid storm: analysis of the nationwide surveys: The taskforce committee of the Japan Thyroid Association and Japan Endocrine Society for the establishment of diagnostic criteria and nationwide surveys for thyroid storm". Clinical Endocrinology. 84 (6): 912–8. doi:10.1111/cen.12949. PMID 26387649. S2CID 3050566. ## External links[edit] Classification D * ICD-10: E05.5 * MeSH: D013958 External resources * eMedicine: article/925147 * v * t * e Thyroid disease Hypothyroidism * Iodine deficiency * Cretinism * Congenital hypothyroidism * Myxedema * Myxedema coma * Euthyroid sick syndrome * Signs and symptoms * Queen Anne's sign * Woltman sign * Thyroid dyshormonogenesis * Pickardt syndrome Hyperthyroidism * Hyperthyroxinemia * Thyroid hormone resistance * Familial dysalbuminemic hyperthyroxinemia * Hashitoxicosis * Thyrotoxicosis factitia * Thyroid storm Graves' disease * Signs and symptoms * Abadie's sign of exophthalmic goiter * Boston's sign * Dalrymple's sign * Stellwag's sign * lid lag * Griffith's sign * Möbius sign * Pretibial myxedema * Graves' ophthalmopathy Thyroiditis * Acute infectious * Subacute * De Quervain's * Subacute lymphocytic * Palpation * Autoimmune/chronic * Hashimoto's * Postpartum * Riedel's Enlargement * Goitre * Endemic goitre * Toxic nodular goitre * Toxic multinodular goiter * Thyroid nodule * Colloid nodule [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: 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 storm	c0040127	3,931	wikipedia	https://en.wikipedia.org/wiki/Thyroid_storm	2021-01-18T18:39:08	{"mesh": ["D013958"], "umls": ["C0040127"], "wikidata": ["Q4458080"]}
Glioblastoma is a malignant (cancerous) brain tumor that develops from a specific type of brain cell called an astrocyte. These cells help support and nourish neurons (nerve cells of the brain) and form scar tissue that helps repair brain damage in response to injury. Glioblastomas are often very aggressive and grow into surrounding brain tissue. Signs and symptoms, such as headache, nausea, vomiting and/or drowsiness, may develop when the tumor begins to put excess pressure on the brain. Affected people may also experience other features depending on the size and location of the tumor. In most cases, the exact underlying cause is unknown; however, they can rarely occur in people with certain genetic syndromes such as neurofibromatosis type 1, Turcot syndrome and Li Fraumeni syndrome. There is currently no cure for glioblastoma. Treatment is palliative and may include surgery, radiation therapy and/or chemotherapy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Glioblastoma	c0017636	3,932	gard	https://rarediseases.info.nih.gov/diseases/2491/glioblastoma	2021-01-18T18:00:19	{"mesh": ["D005909"], "synonyms": ["Glioblastoma multiforme", "Giant cell glioblastoma (histologic variant)", "Gliosarcoma (histologic variant)"]}
TRNT1 deficiency is a condition that affects many body systems. Its signs and symptoms can involve blood cells, the immune system, the eyes, and the nervous system. The severity of the signs and symptoms vary widely. A common feature of TRNT1 deficiency is a blood condition called sideroblastic anemia, which is characterized by a shortage of red blood cells (anemia). In TRNT1 deficiency, the red blood cells that are present are unusually small (erythrocytic microcytosis). In addition, developing red blood cells in the bone marrow (erythroblasts) can have an abnormal buildup of iron that appears as a ring of blue staining in the cell after treatment in the lab with certain dyes. These abnormal cells are called ring sideroblasts. Many people with TRNT1 deficiency have an immune system disorder (immunodeficiency) that can lead to recurrent bacterial infections. Repeated infections can cause life-threatening damage to internal organs. The immunodeficiency is characterized by low numbers of immune system cells called B cells, which normally help fight infections by producing immune proteins called antibodies (or immunoglobulins). These proteins target foreign invaders such as bacteria and viruses and mark them for destruction. In many individuals with TRNT1 deficiency, the amount of immunoglobulins is also low (hypogammaglobulinemia). In addition, many individuals with TRNT1 deficiency have recurrent fevers that are not caused by an infection. These fever episodes are often one of the earliest recognized symptoms of TRNT1 deficiency, usually beginning in infancy. The fever episodes are typically accompanied by poor feeding, vomiting, and diarrhea, and can lead to hospitalization. In many affected individuals, the episodes occur regularly, arising approximately every 2 to 4 weeks and lasting 5 to 7 days, although the frequency can decrease with age. Eye abnormalities, often involving the light-sensing tissue at the back of the eye (the retina), can occur in people with TRNT1 deficiency. Some of these individuals have a condition called retinitis pigmentosa, in which the light-sensing cells of the retina gradually deteriorate. Eye problems in TRNT1 deficiency can lead to vision loss. Neurological problems are also frequent in TRNT1 deficiency. Many affected individuals have delayed development of speech and motor skills, such as sitting, standing, and walking, and some have low muscle tone (hypotonia). Features that occur less commonly in people with TRNT1 deficiency include hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss), recurrent seizures (epilepsy), and problems with the kidneys or heart. TRNT1 deficiency encompasses what was first thought to be two separate disorders, a severe disorder called sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) and a milder disorder called retinitis pigmentosa with erythrocytic microcytosis (RPEM), each named for its most common features. SIFD begins in infancy, and affected individuals usually do not survive past childhood. RPEM, on the other hand, is recognized in early adulthood, and the microcytosis usually does not cause any health problems. However, it has since been recognized that some individuals have a combination of features that fall between these two ends of the severity spectrum. All of these cases are now considered part of TRNT1 deficiency. ## Frequency TRNT1 deficiency is a rare condition; its prevalence is unknown. Approximately 20 affected individuals have been described in the medical literature. ## Causes TRNT1 deficiency is caused by mutations in the TRNT1 gene, which provides instructions for making a protein involved in the production (synthesis) of other proteins. During protein synthesis, a molecule called transfer RNA (tRNA) helps assemble protein building blocks (amino acids) into a chain that forms the protein. Each tRNA carries a specific amino acid to the growing chain. The TRNT1 protein modifies tRNAs, which allows the correct amino acid to be attached to each tRNA. TRNT1 gene mutations lead to a shortage (deficiency) of functional TRNT1 protein. As a result, modification of tRNA molecules is impaired. Without the modification, tRNAs are thought to be less able to participate in protein synthesis. Researchers suspect that protein synthesis in cellular structures called mitochondria, which are the energy-producing centers of cells, is most strongly affected. The resulting decrease in energy production may damage cells in many body systems, leading to the varied signs and symptoms of TRNT1 deficiency. Researchers believe that mutations that cause a greater impairment of TRNT1 function lead to more severe signs and symptoms. ### Learn more about the gene associated with TRNT1 deficiency * TRNT1 ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	TRNT1 deficiency	c4310776	3,933	medlineplus	https://medlineplus.gov/genetics/condition/trnt1-deficiency/	2021-01-27T08:24:41	{"gard": ["667"], "omim": ["616959", "616084"], "synonyms": []}
An X-linked syndromic intellectual disability characterized by intellectual disability, subcortical cerebral atrophy, dental anomalies, patella luxation, lower back skin dimple, and dysmorphic facial features. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: 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 intellectual disability-dysmorphism-cerebral atrophy syndrome	c1839730	3,934	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2958	2021-01-23T16:59:34	{"gard": ["4482"], "mesh": ["C535274"], "omim": ["309610"], "umls": ["C1839730"], "synonyms": ["Prieto-Badia-Mulas syndrome"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Language-based learning disability" – news · newspapers · books · scholar · JSTOR (November 2012) (Learn how and when to remove this template message) Language-based learning disabilities or LBLD are "heterogeneous" neurological differences that can affect skills such as listening, reasoning, speaking, reading, writing, and math calculations.[1] It is also associated with movement, coordination, and direct attention. LBLD is not usually identified until the child reaches school age. Most people with this disability find it hard to communicate, to express ideas efficiently and what they say may be ambiguous and hard to understand[2] It is [1] a neurological difference. It is often hereditary, and is frequently associated to specific language problems.[3] There are two types of learning disabilities: non-verbal, which includes disabilities from psychomotor difficulties to dyscalculia, and verbal, language based.[4][5] ## Contents * 1 Symptoms * 2 Prevalence * 3 Diagnosis * 3.1 Dyslexia * 4 Prognosis * 5 Treatment * 6 See also * 7 References * 8 External links ## Symptoms[edit] LBLD consists of dyscalculia which comprises the reading of numbers sequentially, learning the time table, and telling time;[6] dyslexia; and difficulties associated with written language such as trouble learning new vocabulary, letters and alphabets. Auditory processing disorders can cause trouble understanding questions and following directions, understanding and remembering the details of a story's plot or a classroom lecture, learning words to songs and rhymes, telling left from right, and having a hard time with reading and writing .[7] Difficulties associated with reading and spoken language involve trouble understanding questions and following directions, understanding and retaining the details of a story's plot or a classroom lecture, nonword repetition, learning words to songs and rhymes, and identifying the sounds that correspond to letters, which makes learning to read difficult[8] Difficulties associated with motor skills include difficulty telling left from right which is part of motor incoordination, visual perceptual problems, and memory problem[9] ## Prevalence[edit] 15–20% of the children in the United States have a language-based learning disability. Of the students with specific learning disabilities receiving special education services, 70–80% have a discrepancy in reading.[10] ## Diagnosis[edit] A speech-language pathologist (SLP), psychologist, social worker, and sometimes neurologist work together or individually to find the proper diagnosis for children with LBLD. Additionally, they evaluate speaking, listening, reading, and written language for children who have LBLD. * SLPs evaluate the child's comprehension skills, and the child's ability to follow verbal and written directions. Also, they look for responsiveness, and see if the child recognizes familiar signs or holds a book correctly and they look for whether the child knows and/or writes letters, and names. * Social workers obtain literacy history from the home, and then observe the child during classroom activities, they look for social interactions. * Psychologists review a child's phonological memory by having him or her repeat series of words, numbers, letters, and sounds. They also look for response from the child to environmental and social factors. * Neurologists look for motor skills, brain functions which include visual and auditory perception.[11] ### Dyslexia[edit] Dyslexia is a common language-based learning disability. Dyslexia can affect reading fluency, decoding, reading comprehension, recall, writing, spelling, and sometimes speech and can exist along with other related disorders.[12] The greatest difficult those with the disorder have is with spoken and the written word. These issues present pertain but are not limited to: * Expressing ideas clearly, as if the words needed are on the tip of the tongue but won't come out. * Letters and numbers * Learning the alphabet * Mixing up the order of numbers that are a part of math calculations * Spelling * Memorizing the times tables * Telling time[3] ## Prognosis[edit] LBLD can be an enduring problem. Some people might experience overlapping learning disabilities that make improvement problematic. Others with single disabilities often show more improvement. Most subjects can achieve literacy via coping mechanisms and education. ## Treatment[edit] Special education classes are the primary treatment. These classes focus on activities that sustain growth in language skills. The foundation of this treatment is repetition of oral, reading and writing activities. Usually the SLP, psychologist and the teacher work together with the children in small groups in the class room. Another treatment is looking at a child's needs through the Individual Education Plan (IEP). In this program teachers and parents work together to monitor the progress of the child's comprehensive, verbal, written, social, and motor skills in school and in the home. Then the child goes through different assessments to determine his/her level. The level that the child is placed in will determine the class size, number of teachers, and the need for therapy. ## See also[edit] * Auditory processing disorder * Developmental verbal dyspraxia * Specific language impairment ## References[edit] 1. ^ a b Vinson, Betsy Partin. (2006). Language Disorders Across the Lifespan. Belmont: Cengage Demar. ISBN 978-1-4180-0954-0. 2. ^ M.B. Aria. Learn How To Be A Better Parent And Raise Healthy Happy Children 3. ^ a b "Language-Based Learning Disabilities (Reading, Spelling, and Writing)". American Speech-Language-Hearing Association (ASHA). Retrieved August 16, 2016. 4. ^ "An Introduction To Language Based Learning Disabilities". www.parentinged.com. Retrieved August 16, 2016. 5. ^ American Speech-Language-Hearing Association 6. ^ Lerner, Janet W. (2000). Learning disabilities: theories, diagnosis, and teaching strategies. Boston: Houghton Mifflin. ISBN 978-0-395-96114-8. 7. ^ Neuman, Susan B.; David K. Dickinson. (2006). Handbook of Early Literacy Research. Minneapolis: Guilford Publications. ISBN 1 -5938-5184-7. 8. ^ G.M. McArthur; J.H. Hogben; V.T. Edwards; et al. (2000). "On the "specifics" of specific reading disability and specific language impairment". Journal of Child Psychology and Psychiatry. 41 (7): 869–874. doi:10.1111/1469-7610.00674. PMID 11079429. 9. ^ Paul, Rhea, Pamela Bruni, and Ayub Balweel. (2006). Language Disorders from Infancy Through Adolescence: Assessment and Intervention. St. Louis: Mosby. ISBN 978-0-323-03685-6.CS1 maint: multiple names: authors list (link) 10. ^ "Resources for Language-based Learning Differences". Verticy Learning. Archived from the original on October 15, 2009. 11. ^ M.F. Joanisse; F.R. Manis; P. Keating; M.S. Seidenberg (2000). "Language Deficits in Dyslexic Children: Speech Perception, Phonology, and Morphology". Journal of Experimental Child Psychology. 77 (1): 30–60. CiteSeerX 10.1.1.55.2655. doi:10.1006/jecp.1999.2553. PMID 10964458. 12. ^ "Dyslexia". Learning Disabilities Association of America. Retrieved August 16, 2016. ## External links[edit] * Language disability and attention disorder. * Non-Verbal Learning Disability. * Autism Spectrum Disorders. * Dysgraphia. * v * t * e Dyslexia and related specific developmental disorders Conditions Speech, language, and communication * Expressive language disorder * Infantile speech * Landau–Kleffner syndrome * Language disorder * Lisp * Mixed receptive-expressive language disorder * Specific language impairment * Speech and language impairment * Speech disorder * Speech error * Speech sound disorder * Stuttering * Tip of the tongue Learning disability * Dyslexia * Dyscalculia * Dysgraphia * Disorder of written expression Motor * Developmental coordination disorder * Developmental verbal dyspraxia Sensory * Auditory processing disorder * Sensory processing disorder Related topics * Dyslexia research * Irlen filters * Learning Ally * Learning problems in childhood cancer * Literacy * Management of dyslexia * Multisensory integration * Neuropsychology * Reading acquisition * Spelling * Writing system Lists * Dyslexia in fiction * Languages by Writing System * People with dyslexia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Language-based learning disability	None	3,935	wikipedia	https://en.wikipedia.org/wiki/Language-based_learning_disability	2021-01-18T19:06:46	{"wikidata": ["Q17148671"]}
A number sign (#) is used with this entry because of evidence that susceptibility to juvenile absence epilepsy-1 is conferred by variation in the EFHC1 gene (608815) on chromosome 6p12. Susceptibility to juvenile myoclonic epilepsy-1 (EJM1; 254770) is also conferred by variation in the EFHC1 gene. See also EJA2 (see 607628), which is conferred by mutation in the CLCN2 gene (600570) on chromosome 3q26. Clinical Features Juvenile absence epilepsy is a subtype of idiopathic generalized epilepsy (IGE; see 600669). Manifestations occur around puberty, in contrast to childhood absence epilepsy (CAE; 600131), which begins at age 6 to 7 years. Absence seizures, generalized tonic-clonic seizures (GTCS), GTCS on awakening, and myoclonic seizures are the main features of JAE. (Commission on Classification and Terminology of the International League Against Epilepsy, 1989). Obeid (1994) described 15 patients, ranging in age from 11 to 25 years, who suffered from juvenile absence epilepsy. Mean age of onset of absence attacks was 11.4 years. Only 3 of the patients had absence seizures as the only seizure type. Twelve had associated tonic-clonic seizures; 3 of these patients also had sporadic myoclonus. Obeid (1994) studied 14 families with an average of 6 sibs per family. Four of the probands had a sib with epilepsy. Of these 4, 2 had juvenile absence epilepsy, whereas the other 2 were diagnosed as having symptomatic epilepsy, one secondary to infantile hemiplegia and the other considered to be idiopathic generalized tonic-clonic seizures. Inheritance Winawer et al. (2003) studied 84 persons from 31 families with myoclonic or absence seizures and found that 65% (20 families) were concordant for seizure type (myoclonic, absence, or both). In 2 families, all affected members had myoclonic seizures; in 12 families, all affected members had absence seizures; in 2 families, all affected members had myoclonic and absence seizures. The number of families concordant for juvenile myoclonic epilepsy (see 254770) was greater when compared to JAE and CAE, but not when JAE was compared to CAE. Winawer et al. (2003) concluded that there are distinct genetic effects on absence and myoclonic seizures, and suggested that examining seizure types as opposed to syndromes may be more useful in linkage studies. Mapping Sander et al. (2000) used nonparametric multipoint linkage analysis to identify susceptibility loci among 130 IGE-multiplex families ascertained through a proband with childhood or juvenile absence epilepsy or juvenile myoclonic epilepsy, and 1 or more sibs affected by an IGE trait. They obtained evidence for a novel IGE susceptibility locus on chromosome 3q26 with a peak nonparametric linkage (NPL) score of 4.19 at D3S3725 (p = 0.000017). ### Associations Pending Confirmation Sander et al. (1997) used a tetranucleotide repeat polymorphism in the noncoding region of the GRIK1 gene (138245) on chromosome 21q22 to test the hypothesis that allelic variants of this gene confer genetic susceptibility to JAE. Family-based association analysis using the haplotype relative risk statistic revealed an association of JAE with the 9 repeat-containing allele of the GRIK1 tetranucleotide polymorphism. Supportive evidence for linkage to JAE was obtained (maximum lod = 1.67 at GRIK1) under an autosomal dominant mode of inheritance, and significant allele sharing (p less than 0.05) among the affected family members suggested that allelic variants of GRIK1 contribute a major genetic determinant to the pathogenesis of JAE. Molecular Genetics Stogmann et al. (2006) identified mutations in the EFHC1 gene (see, e.g., 608815.0006; 608825.0007) in patients with juvenile absence epilepsy. INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Absence seizures \- Generalized tonic-clonic seizures (GTCS) \- GTCS on awakening \- Myoclonic seizures \- EEG shows 3-4-Hz spike waves MISCELLANEOUS \- Onset around puberty MOLECULAR BASIS \- Caused by mutation in the chloride channel-2 gene (CLCN2, 600570.0003 ) \- Caused by mutation in the EF-hand domain (C-terminal)-containing 1 gene EFHC1, ( 608815.0006 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	EPILEPSY, JUVENILE ABSENCE, SUSCEPTIBILITY TO, 1	c2750892	3,936	omim	https://www.omim.org/entry/607631	2019-09-22T16:08:56	{"doid": ["0111324"], "mesh": ["C535495"], "omim": ["607631"], "orphanet": ["1941"], "synonyms": ["JAE", "Alternative titles", "JAE1"]}
Congenital urachal anomaly (CUA) describes a group of urachal remnants, found more frequently in males than females, that result from incomplete closure of the urachus (an embryological remnant of the allantois) during prenatal development, and that are usually asymptomatic (and found as an incidental finding on a radiological study) but can also present with umbilical discharge (in patent urachus or urachal sinus), infraumblical mass and pain, or with complications such as obstruction and infection. CUAs include patent urachus, urachal sinus, urachal cyst and urachal diverticulum (see these terms). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: 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 urachal anomaly	c1739100	3,937	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=435743	2021-01-23T16:59:01	{"umls": ["C1739100"]}
Primary dystonia DYT2 type is characterized by segmental dystonia that manifests with involuntary posturing affecting predominantly the feet. ## Epidemiology The exact prevalence is unknown. The disease is reported in a limited number of Jewish and Gypsy families. ## Clinical description The onset of the symptoms is early in childhood or adolescence. Progression to generalized dystonia is possible. ## Genetic counseling The DYT2 locus is unknown. Autosomal recessive transmission is suggested. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Primary dystonia, DYT2 type	c1857093	3,938	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99657	2021-01-23T17:37:19	{"gard": ["2028"], "mesh": ["C538006"], "omim": ["224500"], "icd-10": ["G24.1"], "synonyms": ["DYT2"]}
Intrahepatic cholestasis of pregnancy (ICP) is a disorder of the liver that occurs in women during pregnancy. Cholestasis is a condition that impairs the release of bile (a digestive juice) from liver cells. The bile then builds up in the liver, impairing liver function. Symptoms typically become apparent in the third trimester of pregnancy and can include severe itching (pruritus). Occasionally, the skin and the whites of the eyes can have a yellow appearance (jaundice). ICP is additionally associated with risks to the developing baby such as premature delivery and stillbirth. The cause of ICP is largely unknown, although approximately 15% of cases are caused by mutations in either the ABCB11 or ABCB4 genes. Mutations within the ABCB11 and ABCB4 genes are inherited in an autosomal dominant manner. Symptoms of ICP are typically limited to pregnancy. Bile flow returns to normal after delivery and the signs and symptoms of the condition disappear, however, they can return during later pregnancies. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Intrahepatic cholestasis of pregnancy	c0268318	3,939	gard	https://rarediseases.info.nih.gov/diseases/9804/intrahepatic-cholestasis-of-pregnancy	2021-01-18T17:59:45	{"mesh": ["C535932"], "omim": ["147480", "614972"], "umls": ["C0268318"], "orphanet": ["69665"], "synonyms": ["Familial intrahepatic cholestasis of pregnancy", "ICP", "Recurrent intrahepatic cholestasis of pregnancy", "RICP", "Pregnancy related cholestasis", "Familial recurrent intrahepatic cholestasis of pregnancy", "Cholestasis, intrahepatic of pregnancy", "Gravidic intrahepatic cholestasis", "Pregnancy-related cholestasis"]}
Adiposis dolorosa Other namesAnders disease Adiposis dolorosa of the diffuse truncal form (Dercum), The anterior view shows the peculiar apron of fat and the small size of the hands. The posterior view shows the arrangement of fat in folds over the hips. SpecialtyEndocrinology Adiposis dolorosa, is an outdated term for many years used synonymously as Dercum's disease, lipedema or Anders disease.[1] While there are numerous references to Adiposis dolorosa, it is recommended that the term no longer be used. Dercum's is now recognized as a separate condition, as is lipedema.[2][3] ## References[edit] 1. ^ Herbst KL. Subcutaneous Adipose Tissue Diseases: Dercum Disease, Lipedema, Familial Multiple Lipomatosis and Madelung Disease. In: Purnell J, Perreault L, eds. Endotext. Massachusetts: MDText.com; 2019. 2. ^ Cornely M. Lipoedema of arms and legs. Part 2: Conservative and surgical therapy of the lipoedema, Lipohyper- plasia dolorosa. Phlebologie 2011;40:146–151. 3. ^ Herbst K, Mirkovskaya L, Bharhagava A, Chava Y, Te CH. Lipedema Fat and Signs and Symptoms of Illness, Increase with Advancing Stage. Archives of Medicine. 2015;7(4:10):1-8. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Adiposis dolorosa	c0001529	3,940	wikipedia	https://en.wikipedia.org/wiki/Adiposis_dolorosa	2021-01-18T18:43:40	{"gard": ["5750"], "mesh": ["D000274"], "umls": ["C0001529"], "icd-9": ["272.8"], "orphanet": ["36397"], "wikidata": ["Q1615557"]}
Feigenbaum et al. (1990, 1994) described 2 brothers with this combination. The proband presented at age 22 years with deteriorating cognitive function, sensorineural deafness, and proteinuria. At the age of 27 years, diabetes mellitus and renal artery stenosis were diagnosed. Renal biopsy showed glomerular sclerosis and mesangiolysis. Progressive neurologic deterioration with cerebellar symptoms and photomyoclonic seizures ensued. Death occurred at age 31 years. Autopsy showed severe atherosclerosis of renal, coronary, and cerebral arteries and the aorta. Diffuse neuronal loss and gliosis of the cerebral deep gray matter, cerebellum and dentate nuclei were found, as well as scattered infarcts throughout the brain. A brother died at age 26 years with similar clinical and pathologic findings. Studies of 2 sisters and the parents were normal. In vitro studies of cultured skin fibroblasts documented partial deficiencies of complexes 3 and 4 of the mitochondrial respiratory chain. This deficiency was expressed in skin fibroblasts, kidney, and liver, but not in muscle. The findings were thought to be compatible with mitochondrial, autosomal recessive, or X-linked recessive inheritance. Many of the features were similar to those in Herrmann syndrome (172500), but that condition appeared to be autosomal dominant and there were different pathologic findings, namely, PAS-positive deposits in the dentate and olivary nuclei as well as the renal collecting tubules. Neuro \- Cerebral artery atherosclerosis \- Cognitive function loss \- Photomyoclonic seizures \- Cerebellar signs Renal \- Renal artery stenosis Metabolic \- Diabetes mellitus Inheritance \- Autosomal recessive Lab \- Proteinuria Cardiovascular \- Aortic and coronary atherosclerosis Ears \- Sensorineural deafness ▲ 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	ATHEROSCLEROSIS, PREMATURE, WITH DEAFNESS, NEPHROPATHY, DIABETES MELLITUS, PHOTOMYOCLONUS, AND DEGENERATIVE NEUROLOGIC DISEASE	c2931125	3,941	omim	https://www.omim.org/entry/209010	2019-09-22T16:30:37	{"mesh": ["C536178"], "omim": ["209010"], "orphanet": ["1192"]}
For a general phenotypic description and a discussion of genetic heterogeneity of cone-rod dystrophy, see 120970. Clinical Features Kamenarova et al. (2013) studied a 3-generation Romani family segregating autosomal dominant cone-rod dystrophy with a slightly variable but early age of onset, at around 10 years of age. Affected individuals had gradual visual impairment and photophobia; ophthalmoscopy revealed typical signs of CORD including narrowing of retinal vessels, scattered bone-spicule pigmentation in the midperipheral retina, retinal pigment epithelium atrophy, and optic disc pallor. Electroretinography showed reduced photopic and scotopic responses, and visual field examination demonstrated central scotoma. Mapping In a 3-generation Romani family segregating autosomal dominant cone-rod dystrophy (adCORD), in which known loci associated with adCORD had been excluded, Kamenarova et al. (2013) performed a genomewide analysis using short tandem repeat markers and obtained a maximum lod score of 3.31 for a 6.7-Mb region on chromosome 10q26 between markers D10S1757 and D10S1782. An independent genomewide scan using SNP microarray defined a 7.3-Mb region on 10q26, spanning the 6.7-Mb interval highlighted by the original STR markers. Molecular Genetics In a 3-generation Romani family segregating autosomal dominant cone-rod dystrophy (adCORD) mapping to chromosome 10q26, Kamenarova et al. (2013) screened key positional candidate genes but found no pathogenic variants, and high-density oligonucleotide-based array CGH revealed no chromosomal aberration, deletion, or amplification of a part of whole gene. INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Gradual visual impairment \- Photophobia \- Narrowing of retinal vessels \- Scattered bone-spicule pigmentation in midperiphery \- Atrophy of retinal pigment epithelium \- Optic disc pallor \- Reduced photopic and scotopic responses on electroretinography \- Central scotoma MISCELLANEOUS \- Onset of disease around 10 years of age ▲ 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	CONE-ROD DYSTROPHY 17	c3489532	3,942	omim	https://www.omim.org/entry/615163	2019-09-22T15:53:00	{"doid": ["0111023"], "mesh": ["D000071700"], "omim": ["120970", "615163"], "orphanet": ["1872"], "synonyms": []}
This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (June 2019) (Learn how and when to remove this template message) Christianson syndrome SpecialtyMedical genetics CausesMutation in SLC9A6 gene Christianson syndrome is an X linked syndrome associated with intellectual disability, microcephaly, seizures, ataxia and absent speech. ## Contents * 1 Presentation * 2 Genetics * 3 Diagnosis * 3.1 Differential diagnosis * 4 Management * 5 Epidemiology * 6 History * 7 References ## Presentation[edit] Onset of symptoms is normally within the first year of life with truncal ataxia and seizures. The head is small (microcephaly). Common facial abnormalities include[citation needed] * Long narrow face * Prominent nose * Prominent jaw * Large ears * Open mouth * Thick eyebrows Other common features include[citation needed] * Uncontrolled drooling * Abnormal eye movements The associated intellectual disablity is usually in the profound range. Those affected often have a happy demeanor with frequent smiling and spontaneous laughter. ## Genetics[edit] This condition is caused by mutations in the SLC9A6 gene. This gene is located on the long arm of the X chromosome (Xq26.3).The gene encodes a sodium/hydrogen exchanger located in the endosomes. Mutations in this gene cause a rise in the pH of the endosomes.[citation needed] How this causes the clinical features is not known presently. The inheritance of this condition is X-linked dominant. ## Diagnosis[edit] The diagnosis may be suspected on clinical grounds.It is made by sequencing the SLC9A6 gene.[citation needed] ### Differential diagnosis[edit] * Angelman syndrome * Spinocerebellar ataxia type 29 ## Management[edit] There is presently no curative treatment. Management is supportive.[citation needed] ## Epidemiology[edit] The prevalence is not known but this is considered to be a rare disease. ## History[edit] This condition was first described in 1999.[1] The causative mutation was discovered in 2008.[2] ## References[edit] 1. ^ Christianson AL, Stevenson RE, van der Meyden CH, Pelser J, Theron FW, van Rensburg PL, Chandler M, Schwartz CE (1999) X linked severe mental retardation, craniofacial dysmorphology, epilepsy, ophthalmoplegia, and cerebellar atrophy in a large South African kindred is localised to Xq24-q27. J Med Genet 36:759–766 2. ^ Gilfillan GD, Selmer KK, Roxrud I, Smith R, Kyllerman M, Eiklid K, Kroken M, Mattingsdal M, Egeland T, Stenmark H, Sjøholm H, Server A, Samuelsson L, Christianson A, Tarpey P, Whibley A, Stratton MR, Futreal PA, Teague J, Edkins S, Gecz J, Turner G, Raymond FL, Schwartz C, Stevenson RE, Undlien DE, Strømme P (2008) SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome. Am J Hum Genet 82:1003–10 Classification D * ICD-10: Q87.8 * OMIM: 300243 * MeSH: C567484, C537450, C567484 C537450, C567484, C537450, C567484 * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Christianson syndrome	c2678194	3,943	wikipedia	https://en.wikipedia.org/wiki/Christianson_syndrome	2021-01-18T19:03:01	{"gard": ["9155", "10572"], "mesh": ["C537450", "C567484"], "umls": ["C2678194"], "orphanet": ["85278"], "wikidata": ["Q28065629"]}
A number sign (#) is used with this entry because of evidence that Noonan syndrome-8 (NS8) is caused by heterozygous mutation in the RIT1 gene (609591) on chromosome 1q22. Description Noonan syndrome-8 is an autosomal dominant disorder characterized by short stature, distinctive facial features, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. A subset of patients show intellectual disabilities (summary by Aoki et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950). Clinical Features Aoki et al. (2013) reported 17 unrelated individuals with Noonan syndrome-8 who ranged in age from a few months to 15 years. Patients had a distinctive facial appearance with relative macrocephaly, hypertelorism, downslanting palpebral fissures, ptosis, epicanthal folds, and low-set ears. Many had skin and hair anomalies, such as curly hair, hyperelastic skin, and hyperkeratosis. Other features included short stature and short or webbed neck. Twelve individuals (71%) developed hypertrophic cardiomyopathy, 11 (65%) had pulmonic stenosis, and 5 (29%) had atrial septal defects. At least 4 patients had documented intellectual disability. Nine patients showed perinatal abnormalities, including polyhydramnios, nuchal translucency, and chylothorax. One infant with cardiomyopathy and pleural effusion died at age 53 days, and 1 child developed acute lymphoblastic leukemia at age 5 years. Bertola et al. (2014) reported 6 unrelated Brazilian patients with Noonan syndrome-8. The patients had a high frequency of abnormal findings on prenatal ultrasound, mainly polyhydramnios and fetal hydrops, high birthweight (mean of 4,342 g), relative macrocephaly, left ventricular hypertrophy, and ectodermal findings such as curly hair, hyperpigmentation, and wrinkled palms and soles. Short stature and pectus deformity were less frequent than in patients with other forms of Noonan syndrome. The majority of patients did not show apparent intellectual disability, but formal testing was not performed. One patient developed severe and progressive scoliosis; another patient, who also had factor XI deficiency (612416), developed aggressive giant cell lesions in the mandible at age 15 years. Two other patients had autoimmune disorders, Graves disease and systemic lupus erythematosus, respectively. Gos et al. (2014) reported 4 unrelated Polish patients with Noonan syndrome-8. Dysmorphic craniofacial features included hypertelorism, downslanting palpebral fissures, epicanthal folds, low-set ears with thickened helix, and short neck with low posterior hairline. All patients had pulmonary valve stenosis, 3 had septal defects, and 2 had hypertrophic cardiomyopathy. Only 1 patient had short stature. All had mild cognitive impairment manifest as learning difficulties or delayed speech. Using a standardized form, Kouz et al. (2016) recorded clinical features of all 33 RIT1 mutation-positive patients from 28 families. Clinical and genotype data from 36 individuals with RIT1 mutation reported previously were reviewed. In relation to Noonan syndrome of other genetic etiologies, prenatal abnormalities, cardiovascular disease, and lymphatic abnormalities were common in individuals with RIT1 mutation, whereas short stature, intellectual problems, pectus anomalies, and ectodermal findings were less frequent. RIT1 is one of the major genes for Noonan syndrome. The RIT1-associated phenotype differs from other Noonan syndrome subtypes, with a high prevalence of cardiovascular manifestations, especially hypertrophic cardiomyopathy, and lymphatic problems. Calcagni et al. (2016) concurred with the observations of Kouz et al. (2016) and reported that the RIT1 gene was responsible for Noonan syndrome in 6% of the patients they sequenced. All 9 of their Noonan syndrome patients with RIT1 mutations had congenital cardiac defects. Four also had hypertrophic cardiomyopathy, which in 1 case was severe. Zenker and Kutsche (2016) replied and added observations from Cave et al. (2016) and Yaoita et al. (2016), noting that 94% of the more than 120 RIT1 mutation-positive patients had cardiac abnormalities, with pulmonic stenosis (64%), hypertrophic cardiomyopathy (45%), and septal defects (39%) being the most frequent. Inheritance The RIT1 mutations identified by Aoki et al. (2013) in 16 patients with NS8 occurred de novo, consistent with sporadic occurrence of the disorder. One additional patient inherited a heterozygous mutation from a mother with a similar phenotype, suggesting rare autosomal dominant inheritance. DNA was available from the parents of only 2 of the 6 patients with NS8 reported by Bertola et al. (2014); study showed that it was an apparently de novo event in both. Molecular Genetics In 17 (9%) of 180 unrelated patients suspected of having Noonan syndrome but without mutation in selected exons of any known Noonan syndrome-causing genes, Aoki et al. (2013) identified heterozygous mutations in the RIT1 gene (see, e.g., 609591.0001-609591.0004). The first mutations were found by exome sequencing, and subsequent mutations were identified from a larger cohort of patients screened for the RIT1 gene. A total of 9 missense mutations were found. The mutations tended to cluster in the switch II region, and in vitro functional expression studies of 3 of the mutations showed that they resulted in a gain of function. Transfection of 2 of the mutations into zebrafish embryos resulted in a variety of developmental defects, including gastrulation defects, craniofacial abnormalities, pericardial edema, and elongated yolk sac. A smaller percentage of mutant embryos showed even more disorganized growth and abnormal cardiogenesis. The findings were similar to those observed with mutations in other RAS genes (see, e.g., PTPN11, 176876; SOS1, 182530; NRAS, 164790) causing other forms of Noonan syndrome. In 6 (9%) of 70 Brazilian patients with Noonan syndrome but without mutation in selected exons of any known Noonan syndrome-causing genes, Bertola et al. (2014) identified 4 heterozygous missense mutations in the RIT1 gene, all of which had previously been identified in patients with NS8 by Aoki et al. (2013). The mutations were identified by exome sequencing. Bertola et al. (2014) suggested possible hotspots at residues 57 and 95 of the protein due to recurrent mutations, and recommended that RIT1 be added to gene panels for the molecular diagnosis of Noonan syndrome. In 4 unrelated Polish girls with NS8, Gos et al. (2014) identified 3 different heterozygous missense mutations in the RIT1 gene (609591.0004-609591.0006). The mutations in the first 2 patients were found by whole-exome sequencing after mutations in common Noonan syndrome genes were excluded. The mutations in the second 2 patients were found by direct sequencing of the RIT1 gene in 64 patients with Noonan syndrome. Functional studies of the variants were not performed. The RIT1 mutation rate in this study was estimated at 3.8% (4 of 106 Noonan syndrome patients). Kouz et al. (2016) sequenced RIT1 in 310 mutation-negative individuals with a suspected RASopathy and prospectively in individuals who underwent genetic testing for Noonan syndrome. Eleven different RIT1 missense mutations, 3 of which were novel, were identified in 33 subjects from 28 families; codons 57, 82, and 95 represent mutation hotspots. RIT1 is 1 of the 4 most common genes mutated in Noonan syndrome. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature Other \- Failure to thrive HEAD & NECK Head \- Relative macrocephaly Ears \- Low-set ears Eyes \- Hypertelorism \- Epicanthal folds \- Downslanting palpebral fissures \- Ptosis Neck \- Short neck \- Webbed neck CARDIOVASCULAR Heart \- Hypertrophic cardiomyopathy \- Atrial septal defect \- Ventricular septal defect \- Pulmonic stenosis \- Valvular insufficiency GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism SKIN, NAILS, & HAIR Skin \- Hyperelastic skin \- Hyperkeratosis Hair \- Curly hair NEUROLOGIC Central Nervous System \- Intellectual disability (in some patients) PRENATAL MANIFESTATIONS Amniotic Fluid \- Polyhydramnios \- Fetal pleural effusion MISCELLANEOUS \- Onset in utero or at birth \- Most mutations occur de novo \- Features are variable MOLECULAR BASIS \- Caused by mutation in the RIC-like protein without CAAX motif 1 gene (RIT1, 609591.0001 ) ▲ 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	NOONAN SYNDROME 8	c0028326	3,944	omim	https://www.omim.org/entry/615355	2019-09-22T15:52:28	{"doid": ["0060586"], "mesh": ["D009634"], "omim": ["615355"], "orphanet": ["648"], "genereviews": ["NBK1124"]}
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features. In people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items. Hyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others. Impulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting. More than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics. In most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood. ## Frequency Worldwide, ADHD affects approximately 5 percent of children and 3 percent of adults. ## Causes Changes in dozens of genes have been associated with ADHD. Many gene variations, most of which have not been identified, are thought to affect the risk of developing ADHD. Because they are common in many populations worldwide, not all people with these gene variations will have the condition. Many of the gene variations have only a small effect, and most people with ADHD are thought to have numerous associated gene variations. These variations also combine with environmental risk factors to determine an individual's risk of developing this complex condition. Environmental risk factors that may contribute to the development of ADHD include complications during pregnancy and delivery and exposure to heavy metals such as lead. It is unclear how genetic and environmental factors influence each other to contribute to ADHD. Less commonly, ADHD is caused by rare gene mutations or chromosome abnormalities. In these instances, ADHD is usually one of several features of a syndrome that affects multiple parts of the body. In most individuals with ADHD caused by rare gene mutations, a mutation in a single gene is enough to cause the disorder. The genes associated with ADHD are thought to be involved in the development of the brain. The various proteins produced from these genes affect multiple aspects of brain development, including production, growth, or organization of nerve cells (neurons). Other genes associated with ADHD provide instructions for proteins that are important for communication between neurons. Some of these proteins help produce or control the chemicals that relay communication signals between neurons (neurotransmitters). Other proteins have roles at the connections between neurons (synapses) where this communication takes place. The specific ways that changes in associated genes are involved in the development of ADHD are unknown. Research has found that people with ADHD often have low levels of the neurotransmitter dopamine, which has many important functions, including having complex roles in thought (cognition), motivation, behavior, and control of movement. Certain layers of the brain may also develop somewhat differently than usual in people with ADHD. ## Inheritance Pattern ADHD has a tendency to run in families, but the inheritance pattern is usually unknown. Overall, the risk of developing this condition is about nine times greater for first-degree relatives of people with the condition (such as siblings or children) as compared to the general public. People with genetic changes associated with ADHD generally inherit an increased risk of developing the condition, rather than the condition itself. When ADHD is a feature of another genetic syndrome, it can be passed on according to the inheritance pattern of that syndrome. 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Congenital deformity of the chest Pectus excavatum Other namesFunnel chest, dented chest, sunken chest, concave chest, chest hole An example of an extremely severe case of pectus excavatum. SpecialtyOrthopedics Pectus excavatum is a structural deformity of the anterior thoracic wall in which the sternum and rib cage are shaped abnormally. This produces a caved-in or sunken appearance of the chest. It can either be present at birth or develop after puberty. Pectus excavatum can impair cardiac and respiratory function and cause pain in the chest and back. People with the condition may experience severe negative psychosocial effects and avoid activities that expose the chest.[1] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Pathophysiology * 4 Diagnosis * 5 Treatment * 5.1 Conservative treatment * 5.2 Exercise * 5.2.1 Vacuum bell * 5.2.1.1 See also Vacuum Bell * 5.2.2 Orthoses * 5.3 Thoracic surgery * 5.3.1 Magnetic mini-mover procedure * 5.3.2 Ravitch technique * 5.3.3 Nuss procedure * 5.3.4 Robicsek technique * 5.3.5 Taulinoplasty * 5.4 Plastic surgery * 5.4.1 Implants * 5.4.2 Lipofilling * 6 Epidemiology * 7 Etymology * 8 Society * 9 In animals * 10 See also * 11 References * 12 Further reading * 13 External links ## Signs and symptoms[edit] The hallmark of the condition is a sunken appearance of the sternum. The most common form is a cup-shaped concavity, involving the lower end of the sternum; also a broader concavity involving the upper costal cartilages is possible.[2] The lower-most ribs may protrude ("flared ribs").[3] Pectus excavatum defects may be symmetric or asymmetric. People may also experience chest and back pain, which is usually of musculoskeletal origin.[4] In mild cases, cardiorespiratory function is normal, although the heart can be displaced and/or rotated.[5] In severe cases, the right atrium may be compressed, mitral valve prolapse may be present, and physical capability may be limited due to base lung capacity being decreased.[6][7] Psychological symptoms manifest with feelings of embarrassment, social anxiety, shame, limited capacity for activities and communication, negativity, intolerance, frustration, and even depression.[8] ## Causes[edit] Researchers are unsure of the cause of pectus excavatum. Some researchers take the stance that it is a congenital disorder (birth defect) (that is, not genetic) like cleft lip. Others assume that there is some genetic component. A small sample size test found in least some cases, 37% of individuals have an affected first degree family member.[9] As of 2012, a number of genetic markers for pectus excavatum have also been discovered.[10] It was believed for decades that pectus excavatum is caused by an overgrowth of costal cartilage, however people with pectus excavatum actually tend to have shorter, not longer, costal cartilage relative to rib length.[11] Pectus excavatum can be present in other conditions too, including Noonan syndrome, Marfan syndrome[12] and Loeys–Dietz syndrome as well as other connective tissue disorders such as Ehlers–Danlos syndrome.[13] Many children with spinal muscular atrophy develop pectus excavatum due to their diaphragmatic breathing. ## Pathophysiology[edit] Physiologically, increased pressure in utero, rickets and increased traction on the sternum due to abnormalities of the diaphragm have been postulated as specific mechanisms.[9] Because the heart is located behind the sternum, and because individuals with pectus excavatum have been shown to have visible deformities of the heart seen both on radiological imaging and after autopsies, it has been hypothesized that there is impairment of function of the cardiovascular system in individuals with pectus excavatum. While some studies have demonstrated decreased cardiovascular function, no consensus has been reached based on newer physiological tests such as echocardiography of the presence or degree of impairment in cardiovascular function. However, a 2016 meta-analysis found significant evidence that surgical correction of pectus excavatum improves patient cardiac performance.[14] ## Diagnosis[edit] Cross sectional scan of a chest with pectus excavatum Pectus excavatum is initially suspected from visual examination of the anterior chest. Auscultation of the chest can reveal displaced heart beat and valve prolapse. There can be a heart murmur occurring during systole caused by proximity between the sternum and the pulmonary artery.[15] Lung sounds are usually clear yet diminished due to decreased base lung capacity.[16] Many scales have been developed to determine the degree of deformity in the chest wall. Most of these are variants on the distance between the sternum and the spine. One such index is the Backer ratio which grades severity of deformity based on the ratio between the diameter of the vertebral body nearest to xiphosternal junction and the distance between the xiphosternal junction and the nearest vertebral body.[17] More recently the Haller index has been used based on CT scan measurements. An index over 3.25 is often defined as severe.[18] The Haller index is the ratio between the horizontal distance of the inside of the ribcage and the shortest distance between the vertebrae and sternum.[19] Pectus excavatum on PA chest radiograph with shift of heart shadow to the left and radioopacity of the right paracardiac lung field Chest x-rays are also useful in the diagnosis. The chest x-ray in pectus excavatum can show an opacity in the right lung area that can be mistaken for an infiltrate (such as that seen with pneumonia).[20] Some studies also suggest that the Haller index can be calculated based on chest x-ray as opposed to CT scanning in individuals who have no limitation in their function.[21] Pectus excavatum is differentiated from other disorders by a series of elimination of signs and symptoms. Pectus carinatum is excluded by the simple observation of a collapsing of the sternum rather than a protrusion. Kyphoscoliosis is excluded by diagnostic imaging of the spine, where in pectus excavatum the spine usually appears normal in structure.[citation needed] ## Treatment[edit] Pectus excavatum requires no corrective procedures in mild cases.[22] Treatment of severe cases can involve either invasive or non-invasive techniques or a combination of both. Before an operation proceeds several tests are usually performed. These include, but are not limited to, a CT scan, pulmonary function tests, and cardiology exams (such as auscultation and ECGs).[23] After a CT scan is taken, the Haller index is measured. The patient's Haller is calculated by obtaining the ratio of the transverse diameter (the horizontal distance of the inside of the ribcage) and the anteroposterior diameter (the shortest distance between the vertebrae and sternum).[24] A Haller Index of greater than 3.25 is generally considered severe, while normal chest has an index of 2.5.[19][25][26] The cardiopulmonary tests are used to determine the lung capacity and to check for heart murmurs.[citation needed] ### Conservative treatment[edit] The chest wall is elastic, gradually stiffening with age.[27] Non-surgical treatments have been developed that aim at gradually alleviating the pectus excavatum condition, making use of the elasticity of the chest wall, including the costal cartilages, in particular in young cases. ### Exercise[edit] Physical exercise has an important role in conservative pectus excavatum treatment though is not seen as a means to resolve the condition on its own. It is used in order to halt or slow the progression of mild or moderate excavatum conditions[28][29] and as supplementary treatment to improve a poor posture, to prevent secondary complications, and to prevent relapse after treatment.[30] Exercises are aimed at improving posture, strengthening back and chest muscles, and enhancing exercise capacity, ideally also increasing chest expansion.[31] Pectus exercises include deep breathing and breath holding exercises,[28] as well as strength training for the back and chest muscles. Additionally, aerobic exercises to improve cardiopulmonary function are employed.[29] #### Vacuum bell[edit] ##### See also Vacuum Bell[edit] Vacuum bell for pectus excavatum treatment, with hand pump (left) and measuring rod (right) An alternative to surgery, the vacuum bell, was described in 2006; the procedure is also referred to as treatment by cup suction. It consists of a bowl shaped device which fits over the caved-in area; the air is then removed by the use of a hand pump.[32] The vacuum created by this lifts the sternum upwards, lessening the severity of the deformity.[33] It has been proposed as an alternative to surgery in less severe cases.[34] Once the defect visually disappears, two additional years of use of the vacuum bell is required to make what may be a permanent correction.[35][36] The treatment, in combination with physiotherapy exercises, has been judged by some as "a promising useful alternative" to surgery provided the thorax is flexible; the duration of treatment that is required has been found to be "directly linked to age, severity and the frequency of use".[37][38] Long-term results are still lacking.[34][37][38] The vacuum bell can also be used in preparation to surgery.[34][38] #### Orthoses[edit] Brazilian orthopedist Sydney Haje developed a non-surgical protocol for treating pectus carinatum as well as pectus excavatum. The method involves wearing a compressive orthosis and adhering to an exercise protocol.[39] Mild cases have also reportedly been treated with corset-like orthopedic support vests and exercise.[40][41] ### Thoracic surgery[edit] Incentive spirometers deepen lung ventilation after surgery to avoid atelectasis There has been controversy as to the best surgical approach for correction of pectus excavatum. It is important for the surgeon to select the appropriate operative approach based on each individual's characteristics.[42] Surgical correction has been shown to repair any functional symptoms that may occur in the condition, such as respiratory problems or heart murmurs, provided that permanent damage has not already arisen from an extremely severe case.[citation needed][23][dead link] Surgical correction of the pectus excavatum has been shown to significantly improve cardiovascular function;[43] there is inconclusive evidence so far as to whether it might also improve pulmonary function.[44] One of the most popular techniques for repair of pectus excavatum today is the minimally invasive operation, also known as MIRPE or Nuss technique.[45] #### Magnetic mini-mover procedure[edit] The magnetic mini-mover procedure (3MP) is a minimally invasive procedure used to correct pectus excavatum by using two magnets to realign the sternum with the rest of the chest and ribcage.[46] One magnet is inserted 1 cm into the patient's body on the lower end of the sternum, the other is placed externally onto a custom fitted brace. These two magnets generate around 0.04 tesla (T) in order to slowly move the sternum outwards over a number of years. The maximum magnetic field that can be applied to the body safely is around 4 T, making this technique safe from a magnetic viewpoint.[46] The 3MP technique's main advantages are that it is more cost-effective than major surgical approaches such as the Nuss procedure and it is considerably less painful postoperatively. Its effectiveness is limited to younger children in early- to mid-puberty because older individuals have less compliant (flexible) chest walls.[47] One potential adverse interaction with other medical devices is possible inactivation of artificial pacemakers if present. #### Ravitch technique[edit] 26-year-old male after modified-Ravitch reconstruction A visible scar on the chest of a 23-year-old male five years after a successful Ravitch procedure The Ravitch technique is an invasive surgery that was introduced in 1949[48] and developed in the 1950s. It involves creating an incision along the chest through which the cartilage is removed and the sternum detached. A small bar is inserted underneath the sternum to hold it up in the desired position. The bar is left implanted until the cartilage grows back, typically about six months. The bar is subsequently removed in a simple out-patient procedure; this technique is thus a two-stage procedure.[citation needed] The Ravitch technique is not widely practiced because it is so invasive. It is more often used in older individuals, where the sternum has calcified, when the deformity is asymmetrical, or when the less invasive Nuss procedure has proven unsuccessful.[49] #### Nuss procedure[edit] Main article: Nuss procedure X-ray of a 15-year-old male after undergoing the Nuss procedure In 1987, Donald Nuss, based at Children's Hospital of The King's Daughters in Norfolk, Virginia, performed the first minimally invasive repair of pectus excavatum (MIRPE) [50] and presented it much later at a conference in 1997.[50][51][52] His procedure, widely known as the Nuss procedure, involves slipping in one or more concave steel bars into the chest, underneath the sternum. The bar is flipped to a convex position so as to push outward on the sternum, correcting the deformity. The bar usually stays in the body for about two years, although many surgeons are now[when?] moving toward leaving them in for up to five years. When the bones have solidified into place, the bar is removed through outpatient surgery. Although initially designed to be performed in younger children (less than 10 years of age) whose sternum and cartilage is more flexible, there are successful series of Nuss treatment in patients well into their teens and twenties.[citation needed] The Nuss procedure is a two-stage procedure.[citation needed] #### Robicsek technique[edit] In 1965, Francis Robicsek, based at Charlotte Memorial Hospital, now named Carolinas Medical Center in Charlotte, North Carolina, developed the Robicsek procedure. Each time the procedure is performed, it is individually tailored based on the extent and location of the deformity in the patient. The operation begins with an incision, no more than 4–6 centimeters, to the sternum. The pectoralis major muscles are then detached from the sternum. Using the upper limit of the sternal depression as a guide, the deformed cartilages are removed one-by-one, using sharp and blunt dissection. The lower tip of the sternum is then grabbed with a towel-clip and, using blunt dissection, is freed of tissue connections with the pericardium and the pleura. The sternum is then forcefully bent forward into a corrected position. To keep the sternum elevated, a piece of mesh is placed under the mobilized sternum and sutured under moderate tension bilaterally to the stumps of the ribs. The pectoralis muscles are united in front of the sternum and the wound is closed. The Robicsek procedure is a single-stage procedure (one surgery only).[53] The purported advantage of this technique is that it is less invasive than the Ravitch technique, but critics have suggested that the relapse rate may be high due to cartilage and bone displaying memory phenomenon.[42] #### Taulinoplasty[edit] In 2016, Carlos Bardají, a Barcelona-based pediatric surgeon, together with Lluís Cassou, a biomedical engineer, published a paper describing an extra-thoracic surgical procedure for the correction of pectus excavatum called taulinoplasty.[54] A specially designed implant and traction hardware were developed specifically for the procedure. In taulinoplasty, a small hole is drilled into the sternum at the deepest point of defect, and a double screw is driven into the hole. Then, a stainless steel implant is placed underneath the skin on top of the sternum and ribs, centered over the double screw. Traction tools are then used to lift the sternum up by the double screw using the implant and ribs for traction. Additional screws are then used to secure the implant onto the sternum holding the sternum in the desired position. Optionally, stainless steel wire may be wrapped around the implant and ribs to further secure the implant in place. Like the Nuss procedure, taulinoplasty requires follow-up surgery several years later to remove the implanted hardware once the sternum has permanently assumed its new position. The implant and related hardware used in taulinoplasty is a proprietary product of Ventura Medical Technologies and is marketed as a surgical kit under the brand name Pectus UP.[55] Taulinoplasty was developed to be an alternative to the Nuss procedure that eliminates the risks and drawbacks of entering the thorax. In particular, patients usually have shorter operating and recovery times, and less post-operative pain than with the Nuss procedure. ### Plastic surgery[edit] #### Implants[edit] The implant allows pectus excavatum to be treated from a purely morphological perspective. Today it is used as a benchmark procedure as it is simple, reliable, and minimally intrusive while offering aesthetically-pleasing results.[56] This procedure does not, however, claim to correct existing cardiac and respiratory problems which, in very rare cases, can be triggered by the pectus excavatum condition. For female sufferers, the potential resulting breast asymmetry can be partially or completely corrected by this procedure.[57] The process of creating a plaster-cast model, directly on the skin of the patient's thorax, can be used in the design of the implants. The evolution of medical imaging and CAD (computer-aided design)[58] now allows customised 3D implants to be designed directly from the ribcage, therefore being much more precise, easier to place sub-pectorally and perfectly adapted to the shape of each patient.[59] The implants are made of medical silicon rubber which is age-resistant and unbreakable (different to the silicon gel used in breast implants). They will last for life (apart from the case of adverse reactions) and are not visible externally. The surgery is performed under general anesthesia and takes about an hour. The surgeon makes an incision of approximately seven centimetres, prepares the customised space in the chest, inserts the implant deep beneath the muscle, then closes the incision. Post-operative hospitalization is typically around three days. The recovery after the surgery typically requires only mild pain relief. Post-operatively, a surgical dressing is required for several days and compression vest for a month following the procedure. A check-up appointment is carried out after a week for puncture of seroma. If the surgery has minimal complications, the patient can resume normal activities quickly, returning to work after 15 days and participating in any sporting activities after three months. #### Lipofilling[edit] The "lipofilling" technique consists of sucking fat from the patient using a syringe with a large gauge needle (usually from the abdomen or the outer thighs), then after centrifugation, the fat cells are re-injected beneath the skin into whichever hollow it is needed to fill. This technique is primarily used to correct small defects which may persist after conventional surgical treatment. ## Epidemiology[edit] Pectus excavatum occurs in an estimated 1 in 150 to 1 in 1000 births, with male predominance (male-to-female ratio of 3:1). In 35% to 45% of cases family members are affected.[16][60] ## Etymology[edit] Pectus excavatum is from Latin meaning hollowed chest.[61] It is sometimes referred to as sunken chest syndrome, cobbler's chest or funnel chest.[62][63] ## Society[edit] American Olympic swimmer Cody Miller (born 1992) opted not to have treatment for pectus excavatum, even though it limited his lung capacity. He earned a gold medal in 2016.[64][65][66] Professional wrestler Kofi Kingston has not opted for surgery, or ever publicly discussed it. He won his first WWE Championship at WrestleMania 35 after being in the company for 12 years.[67] ## In animals[edit] Pectus excavatum is also known to occur in animals, e.g. the Munchkin breed of cat.[68] Some procedures used to treat the condition in animals have not been used in human treatments, such as the use of a cast with sutures wrapped around the sternum and the use of internal and external splints.[69][70] These techniques are generally used in immature animals with flexible cartilage.[71] ## See also[edit] * Pectus carinatum ## References[edit] 1. ^ "Pectus excavatum". MedLine Plus Medical Encyclopedia. U.S. National Library of Medicine and the National Institutes of Health. 2007-11-12. 2. ^ Blanco FC, Elliott ST, Sandler AD (2011). "Management of congenital chest wall deformities". Seminars in Plastic Surgery (Review). 25 (1): 107–16. doi:10.1055/s-0031-1275177. PMC 3140238. PMID 22294949. 3. ^ See for example Bosgraaf RP, Aronson DC (2010). "Treatment of flaring of the costal arch after the minimally invasive pectus excavatum repair (Nuss procedure) in children". Journal of Pediatric Surgery. 45 (9): 1904–6. doi:10.1016/j.jpedsurg.2010.05.037. PMID 20850643. 4. ^ "Pectus Excavatum Clinical Presentation: History". Medscape. 30 June 2015. Retrieved 7 September 2016. 5. ^ Fokin AA, Steuerwald NM, Ahrens WA, Allen KE (2009). "Anatomical, histologic, and genetic characteristics of congenital chest wall deformities". Seminars in Thoracic and Cardiovascular Surgery (Review). 21 (1): 44–57. doi:10.1053/j.semtcvs.2009.03.001. PMID 19632563. 6. ^ "Cardiopulmonary Manifestations of Pectus Excavatum". Medscape.(subscription required) 7. ^ Jaroszewski, Dawn E.; Warsame, Tahlil A.; Chandrasekaran, Krishnaswamy; Chaliki, Hari (December 2011). "Right Ventricular Compression Observed in Echocardiography from Pectus Excavatum Deformity". Journal of Cardiovascular Ultrasound. 19 (4): 192–195. doi:10.4250/jcu.2011.19.4.192. ISSN 1975-4612. PMC 3259543. PMID 22259662. 8. ^ Brandon, Mike (2016-02-04). "Orthopedic approach to pectus deformities: 32 years of studies". Pectus Excavatum Info. Pediatric Orthopedist and Physiatrist, Orthopectus Clinical Center and Asa Norte Regional Hospital. 2Doctor in Orthopedics, School of Medicine, University de Sāo Paulo, Ribeirāo Preto, SP. Pediatric Orthopedist, Orthopectus Clinical Center. Preceptor, Adult Foot and Pediatric Orthopedics, Federal District Hospital, Brasilia, DF. Retrieved 2016-02-04. 9. ^ a b Shamberger RC (1996). "Congenital chest wall deformities". Current Problems in Surgery (Review). 33 (6): 469–542. doi:10.1016/S0011-3840(96)80005-0. PMID 8641129. 10. ^ Dean C, Etienne D, Hindson D, Matusz P, Tubbs RS, Loukas M (2012). "Pectus excavatum (funnel chest): a historical and current prospective". Surgical and Radiologic Anatomy. 34 (7): 573–9. doi:10.1007/s00276-012-0938-7. PMID 22323132. 11. ^ Eisinger, Robert S.; Harris, Travis; Rajderkar, Dhanashree A.; Islam, Saleem (2019-03-01). "Against the Overgrowth Hypothesis: Shorter Costal Cartilage Lengths in Pectus Excavatum". Journal of Surgical Research. 235: 93–97. doi:10.1016/j.jss.2018.09.080. ISSN 0022-4804. PMID 30691856. 12. ^ "eMedicine — Marfan Syndrome". Harold Chen. 2018-05-23. 13. ^ Creswick HA1, Stacey MW, Kelly RE Jr, Gustin T, Nuss D, Harvey H, Goretsky MJ, Vasser E, Welch JC, Mitchell K, Proud VK (October 2006). "Family study of the inheritance of pectus excavatum". Journal of Pediatric Surgery. 41 (10): 1699–703. doi:10.1016/j.jpedsurg.2006.05.071. PMID 17011272.CS1 maint: multiple names: authors list (link) 14. ^ Maagaard M, Heiberg J (2016). "Improved cardiac function and exercise capacity following correction of pectus excavatum: a review of current literature". Annals of Cardiothoracic Surgery (Review). 5 (5): 485–492. doi:10.21037/acs.2016.09.03. PMC 5056930. PMID 27747182. 15. ^ Guller B, Hable K (1974). "Cardiac findings in pectus excavatum in children: review and differential diagnosis". Chest. 66 (2): 165–71. doi:10.1378/chest.66.2.165. PMID 4850886. Archived from the original on 2008-12-08. 16. ^ a b "eMedicine — Pectus Excavatum". Andre Hebra. 2018-09-18. 17. ^ BACKER OG, BRUNNER S, LARSEN V (1961). "The surgical treatment of funnel chest. Initial and follow-up results". Acta Chirurgica Scandinavica. 121: 253–61. PMID 13685690. 18. ^ Jeannette Diana-Zerpa; Nancy Thacz Browne; Laura M. Flanigan; Carmel A. McComiskey; Pam Pieper (2006). Nursing Care of the Pediatric Surgical Patient (Browne, Nursing Care of the Pediatric Surgical Patient). Sudbury, Mass: Jones & Bartlett Publishers. p. 253. ISBN 978-0-7637-4052-8. 19. ^ a b Haller JA, Kramer SS, Lietman SA (1987). "Use of CT scans in selection of patients for pectus excavatum surgery: a preliminary report". Journal of Pediatric Surgery. 22 (10): 904–6. doi:10.1016/S0022-3468(87)80585-7. PMID 3681619. 20. ^ Hoeffel JC, Winants D, Marcon F, Worms AM (1990). "Radioopacity of the right paracardiac lung field due to pectus excavatum (funnel chest)". Röntgen-Blätter. 43 (7): 298–300. PMID 2392647. 21. ^ Mueller C, Saint-Vil D, Bouchard S (2008). "Chest x-ray as a primary modality for preoperative imaging of pectus excavatum". Journal of Pediatric Surgery. 43 (1): 71–3. doi:10.1016/j.jpedsurg.2007.09.023. PMID 18206458. 22. ^ Klingman, RM (2011). Nelson Texbook of Pediatrics. Philadelphia, PA: Elsevier. 23. ^ a b Crump HW (1992). "Pectus excavatum". Am Fam Physician (Review). 46 (1): 173–9. PMID 1621629. 24. ^ "How the Haller is measured. Departament of Cardiology and Pulmonology of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – Thoracic Surgery Sector" (PDF). 25. ^ "The Nuss procedure for pectus excavatum correction \| AORN Journal". Barbara Swoveland, Clare Medrick, Marilyn Kirsh, Kevin G. Thompson, Nussm Donald. 2001. 26. ^ "Pectus Excavatum overview" (PDF). CIGNA. 27. ^ "Lung elasticity, thorax and age". Archived from the original on 2 May 2016. Retrieved 14 April 2016. 28. ^ a b Peter Mattei (15 February 2011). Fundamentals of Pediatric Surgery. Springer Science & Business Media. p. 315. ISBN 978-1-4419-6643-8. 29. ^ a b Anton H. Schwabegger (15 September 2011). Congenital Thoracic Wall Deformities: Diagnosis, Therapy and Current Developments. Springer Science & Business Media. p. 118. ISBN 978-3-211-99138-1. 30. ^ George W. Holcomb III; Jerry D Murphy; Daniel J Ostlie (31 January 2014). Ashcraft's Pediatric Surgery. Elsevier Health Sciences. p. 270. ISBN 978-0-323-18736-7. 31. ^ Lewis Spitz; Arnold Coran (21 May 2013). Operative Pediatric Surgery, Seventh Edition. CRC Press. p. 251. ISBN 978-1-4441-1715-8. 32. ^ chkd, Norfolk, VA: Children's Hospital of the King's Daughters, archived from the original on 2013-10-11 33. ^ Haecker, FM; Mayr J (April 2006). "The vacuum bell for treatment of pectus excavatum: an alternative to surgical correction?". European Journal of Cardio-Thoracic Surgery. 29 (4): 557–561. doi:10.1016/j.ejcts.2006.01.025. PMID 16473516. 34. ^ a b c Brochhausen C, Turial S, Müller FK, Schmitt VH, Coerdt W, Wihlm JM, Schier F, Kirkpatrick CJ (2012). "Pectus excavatum: history, hypotheses and treatment options". Interactive Cardiovascular and Thoracic Surgery (Review). 14 (6): 801–6. doi:10.1093/icvts/ivs045. PMC 3352718. PMID 22394989. 35. ^ Non-surgical sunken chest treatment device may eliminate surgery, Mass Device, November 2012 36. ^ Raver-Lampman (November 2012), First patients in US receive non-surgical device of sunken chest syndrome, AAAS 37. ^ a b Lopez M, Patoir A, Costes F, Varlet F, Barthelemy JC, Tiffet O (2016). "Preliminary study of efficacy of cup suction in the correction of typical pectus excavatum". Journal of Pediatric Surgery (Review). 51 (1): 183–7. doi:10.1016/j.jpedsurg.2015.10.003. PMID 26526206. 38. ^ a b c Haecker FM, Sesia S (2016). "Non-surgical treatment of pectus excavatum". Journal of Visualized Surgery. 2: 63. doi:10.21037/jovs.2016.03.14. PMC 5638434. PMID 29078491. 39. ^ Haje SA, de Podestá Haje D (2009). "Orthopedic Approach to Pectus Deformities: 32 Years of Studies". Revista Brasileira de Ortopedia. 44 (3): 191–8. doi:10.1016/S2255-4971(15)30067-7. PMC 4783668. PMID 27004171. 40. ^ "LaceIT PE Brace". Advanced Orthotic Designs, Inc. 41. ^ "Orthopectus". Dr. Sydney A. Haje, Ortopedista. 42. ^ a b Robicsek, Hebra (2009). "To Nuss or not to Nuss? Two opposing views". Semin. Thorac. Cardiovasc. Surg. 21 (1): 85–88. doi:10.1053/j.semtcvs.2009.03.007. PMID 19632567. 43. ^ Malek MH, Berger DE, Housh TJ, Marelich WD, Coburn JW, Beck TW (2006). "Cardiovascular function following surgical repair of pectus excavatum: a metaanalysis". Chest (Meta-Analysis). 130 (2): 506–16. doi:10.1378/chest.130.2.506. PMID 16899852. 44. ^ Malek MH, Berger DE, Marelich WD, Coburn JW, Beck TW, Housh TJ (2006). "Pulmonary function following surgical repair of pectus excavatum: a meta-analysis". European Journal of Cardio-Thoracic Surgery (Meta-Analysis). 30 (4): 637–43. doi:10.1016/j.ejcts.2006.07.004. PMID 16901712. 45. ^ Hebra A (2009). "Minimally invasive repair of pectus excavatum". Semin Thorac Cardiovasc Surg (Review). 21 (1): 76–84. doi:10.1053/j.semtcvs.2009.04.005. PMC 5637818. PMID 19632566. 46. ^ a b Harrison MR, Estefan-Ventura D, et al. (January 2007). "Magnetic Mini-Mover Procedure for pectus excavatum: I. Development, design, and simulations for feasibility and safety" (PDF). Journal of Pediatric Surgery. 42 (1): 81–85. doi:10.1016/j.jpedsurg.2006.09.042. PMID 17208545. Retrieved 2008-04-23. 47. ^ Harrison, MR; Michael R. Harrison; Kelly D. Gonzales; Barbara J. Bratton; Darrell Christensen; Patrick F. Curran; Richard Fechter; Shinjiro Hirose (January 2012). "Magnetic mini-mover procedure for pectus excavatum III: safety and efficacy in a Food and Drug Administration-sponsored clinical trial". Journal of Pediatric Surgery. 47 (1): 154–9. doi:10.1016/j.jpedsurg.2011.10.039. PMID 22244409. 48. ^ Ravitch MM (April 1949). "The Operative Treatment of Pectus Excavatum". Ann Surg. 129 (4): 429–44. doi:10.1097/00000658-194904000-00002. PMC 1514034. PMID 17859324. 49. ^ Theresa D. Luu MD (November 2009). "Surgery for Recurrent Pectus Deformities". The Annals of Thoracic Surgery. 88 (5): 1627–1631. doi:10.1016/j.athoracsur.2009.06.008. PMID 19853122. 50. ^ a b Adam J. Białas; Bogumiła Kempińska-Mirosławska (2013). "Minimally invasive repair of pectus excavatum (the Nuss procedure) in Poland and worldwide – a summary of 25 years of history" (PDF). Kardiochirurgia i Torakochirurgia Polska. 10 (1): 42–47. doi:10.5114/kitp.2013.34304. Retrieved 13 April 2016. 51. ^ Nuss D, Kelly RE Jr, Croitoru DP, Katz ME (April 1998). "A 10-year review of a minimally invasive technique for the correction of pectus excavatum". J Pediatr Surg. 33 (4): 545–52. doi:10.1016/S0022-3468(98)90314-1. PMID 9574749. 52. ^ Pilegaard, HK; Licht PB (February 2008). "Early results following the Nuss operation for pectus excavatum—a single-institution experience of 383 patients". Interactive Cardiovascular and Thoracic Surgery. 7 (1): 54–57. doi:10.1510/icvts.2007.160937. PMID 17951271. Retrieved 2008-04-18. 53. ^ Robiscek, Francis. "Marlex Mesh Support For The Correction Of Very Severe And Recurrent Pectus Excavatum". 26 (1): 80–83. Cite journal requires `\|journal=` (help) 54. ^ Bardají, Carlos; Cassou, Lluís (12 September 2016). "Taulinoplasty: the traction technique—a new extrathoracic repair for pectus excavatum". Annals of Cardiothoracic Surgery. 5 (5): 519–522. doi:10.21037/acs.2016.09.07. PMC 5056940. PMID 27747186. 55. ^ "Pectus UP surgery kit, the solution for Pectus Excavatum" (PDF). Ventura Medical Technologies. Retrieved 29 November 2019. 56. ^ André, M. Dahan, E. Bozonnet, I. Garrido, J.-L. Grolleau, J.-P. Chavoin; Pectus excavatum : correction par la technique de comblement avec mise en place d’une prothèse en silicone sur mesure en position rétromusculaire profonde; Encycl Méd Chir, Elsevier Masson SAS - Techniques chirurgicales - Chirurgie plastique reconstructrice et esthétique, 45-671, Techniques chirurgicales - Thorax, 42-480, 2010. 57. ^ Ho Quoc Ch, Chaput B, Garrido I, André A, Grolleau JL, Chavoin JP; Management of breast asymmetry associated with primary funnel chest; Ann Chir Plast Esthet. Elsevier Masson SAS; 2012 Aug 8:1–6. 58. ^ "Pectus Excavatum & Poland Syndrome treatment I AnatomikModeling". 59. ^ J-P. Chavoin, A.André, E.Bozonnet, A.Teisseyre, J..Arrue, B. Moreno, D. Glangloff, J-L. Grolleau, I.Garrido; Mammary implant selection or chest implants fabrication with computer help; Ann.de chirurgie plastique esthétique (2010) 55,471-480. 60. ^ "Pectus Excavatum: Frequently Asked Questions: Surgery: UI Health Topics". Harold M. Burkhart and Joan Ricks-McGillin. 61. ^ chief lexicographer: Douglas M. Anderson (2003). "Pectus Excavatum". Dorland's Medical Dictionary (28 ed.). Philadelphia, Penns.: Saunders. ISBN 978-0-7216-0146-5. Archived from the original on 2009-01-21. Retrieved 2017-05-24. 62. ^ "Pectus Excavatum". 63. ^ Spence, Roy A. J.; Patrick J. Morrison (2005). Genetics for Surgeons. Remedica Publishing. ISBN 978-1-901346-69-5. 64. ^ {{ \|url= http://www.raredr.com/news/rare-disease-rio-cm}} 65. ^ Cody Miller Archived 2015-04-02 at the Wayback Machine – National Team swimmer profile at USASwimming.org 66. ^ Woods, David (27 June 2016). "Cody Miller is IU's first U.S. Olympic swimmer in 40 years". Indianapolis Star. Retrieved 9 August 2016. 67. ^ {{\|url= https://www.distractify.com/p/kofi-kingston-chest-accident \|accessdate=11 August 2019\|publisher=Distractify\|date=23 July 2019}} 68. ^ "Genetic Anomalies of Cats". 69. ^ Fossum, TW; Boudrieau RJ; Hobson HP; Rudy RL (1989). "Surgical correction of pectus excavatum, using external splintage in two dogs and a cat". Journal of the American Veterinary Medical Association. 195 (1): 91–7. PMID 2759902. 70. ^ Risselada M, de Rooster H, Liuti T, Polis I, van Bree H (2006). "Use of internal splinting to realign a noncompliant sternum in a cat with pectus excavatum". Journal of the American Veterinary Medical Association. 228 (7): 1047–52. doi:10.2460/javma.228.7.1047. PMID 16579783. 71. ^ McAnulty JF, Harvey CE (1989). "Repair of pectus excavatum by percutaneous suturing and temporary external coaptation in a kitten". Journal of the American Veterinary Medical Association. 194 (8): 1065–7. PMID 2651373. ## Further reading[edit] * Tocchioni F, Ghionzoli M, Messineo A, Romagnoli P (2013). "Pectus excavatum and heritable disorders of the connective tissue". Pediatric Reports (Review). 5 (3): e15. doi:10.4081/pr.2013.e15. PMC 3812532. PMID 24198927. * Jaroszewski D, Notrica D, McMahon L, Steidley DE, Deschamps C (2010). "Current management of pectus excavatum: a review and update of therapy and treatment recommendations". Journal of the American Board of Family Medicine (Review). 23 (2): 230–9. doi:10.3122/jabfm.2010.02.090234. PMID 20207934. * [1] ## External links[edit] Classification D * ICD-10: Q67.6 * ICD-9-CM: 754.81 * OMIM: 169300 * MeSH: D005660 * DiseasesDB: 29401 External resources * MedlinePlus: 003320 * eMedicine: ped/2558 Wikimedia Commons has media related to Pectus excavatum. Look up pectus in Wiktionary, the free dictionary. * Pectus excavatum at Curlie * v * t * e Congenital malformations and deformations of musculoskeletal system / musculoskeletal abnormality Appendicular limb / dysmelia Arms clavicle / shoulder * Cleidocranial dysostosis * Sprengel's deformity * Wallis–Zieff–Goldblatt syndrome hand deformity * Madelung's deformity * Clinodactyly * Oligodactyly * Polydactyly Leg hip * Hip dislocation / Hip dysplasia * Upington disease * Coxa valga * Coxa vara knee * Genu valgum * Genu varum * Genu recurvatum * Discoid meniscus * Congenital patellar dislocation * Congenital knee dislocation foot deformity * varus * Club foot * Pigeon toe * valgus * Flat feet * Pes cavus * Rocker bottom foot * Hammer toe Either / both fingers and toes * Polydactyly / Syndactyly * Webbed toes * Arachnodactyly * Cenani–Lenz syndactylism * Ectrodactyly * Brachydactyly * Stub thumb reduction deficits / limb * Acheiropodia * Ectromelia * Phocomelia * Amelia * Hemimelia multiple joints * Arthrogryposis * Larsen syndrome * RAPADILINO syndrome Axial Skull and face Craniosynostosis * Scaphocephaly * Oxycephaly * Trigonocephaly Craniofacial dysostosis * Crouzon syndrome * Hypertelorism * Hallermann–Streiff syndrome * Treacher Collins syndrome other * Macrocephaly * Platybasia * Craniodiaphyseal dysplasia * Dolichocephaly * Greig cephalopolysyndactyly syndrome * Plagiocephaly * Saddle nose Vertebral column * Spinal curvature * Scoliosis * Klippel–Feil syndrome * Spondylolisthesis * Spina bifida occulta * Sacralization Thoracic skeleton ribs: * Cervical * Bifid sternum: * Pectus excavatum * Pectus carinatum Authority control * GND: 4186076-7 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Pectus excavatum	c0016842	3,946	wikipedia	https://en.wikipedia.org/wiki/Pectus_excavatum	2021-01-18T18:36:51	{"mesh": ["D005660"], "umls": ["C0016842"], "icd-9": ["754.81"], "icd-10": ["Q67.6"], "wikidata": ["Q431168"]}
Hereditary fibrosing poikiloderma-tendon contractures-myopathy-pulmonary fibrosis syndrome is a rare, genetic, hereditary poikiloderma syndrome characterized by early-onset poikiloderma (mainly on the face), hypotrichosis, hypohidrosis, muscle and tendon contractures with varus foot deformity, progressive proximal and distal muscle weakness in all extremities, and progressive pulmonary fibrosis. Mild lymphedema of the extremities, growth retardation, liver impairment, exocrine pancreatic insufficiency and hematologic abnormalities are additional variable features. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: 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 fibrosing poikiloderma-tendon contractures-myopathy-pulmonary fibrosis syndrome	c3810325	3,947	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=221043	2021-01-23T17:57:49	{"omim": ["615704"], "icd-10": ["Q82.8"], "synonyms": ["POIKTMP syndrome"]}
## Clinical Features In a male and female sib pair of Sikh origin and a male offspring of first-cousin Pakistani Muslims, Al-Gazali et al. (1988) described a combination of Hirschsprung disease (megacolon), hypoplastic nails, and minor dysmorphic facial features. In 1 male infant, bilateral hydronephrosis was detected on routine ultrasound in midtrimester, and imperforate anus was noted at birth. Vesicostomy was performed for an obstructed bladder thought to be the result of posterior urethral valves. A left inguinal hernia was repaired during surgery for Hirschsprung disease. All 3 patients died as infants. GU \- Hydronephrosis Inheritance \- Autosomal recessive Nails \- Hypoplastic nails Abdomen \- Inguinal hernia HEENT \- Minor dysmorphic facies GI \- Hirschsprung megacolon \- Imperforate anus ▲ 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	HIRSCHSPRUNG DISEASE WITH HYPOPLASTIC NAILS AND DYSMORPHIC FACIAL FEATURES	c1856110	3,948	omim	https://www.omim.org/entry/235760	2019-09-22T16:27:07	{"mesh": ["C535615"], "omim": ["235760"], "orphanet": ["2153"]}
Gray platelet syndrome (GPS) is a rare inherited bleeding disorder characterized by platelets that have a gray appearance, severe thrombocytopenia, myelofibrosis, and splenomegaly. About 60 cases from various populations around the world have been described in the literature to date. GPS results from the absence or reduction of alpha-granules in platelets, which store proteins that promote platelet adhesiveness and wound healing when secreted during an injury. GPS is caused by mutations in the NBEAL2 gene and 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	Gray platelet syndrome	c0272302	3,949	gard	https://rarediseases.info.nih.gov/diseases/2562/gray-platelet-syndrome	2021-01-18T18:00:12	{"mesh": ["D055652"], "omim": ["139090"], "orphanet": ["721"], "synonyms": ["GPS", "Platelet alpha-granule deficiency", "Marked decrease or absence of alpha-granules and of platelet-specific alpha-granule proteins"]}
A number sign (#) is used with this entry because susceptibility to bacteremia-2 is caused by variation in the CISH gene (602441). Clinical Features Between 1998 and 2002, Berkley et al. (2005) cultured blood on admission from 19,339 inpatients under the age of 13 years and calculated the incidence of bacteremia on the basis of the population served by a rural district hospital in Kenya. Of 1,783 infants under 60 days old, 228 (12.8%) had bacteremia, as did 866 (5.9%) of 14,787 infants 60 or more days old. Among infants under 60 days old, Escherichia coli and group B streptococci predominated among a broad range of isolates (14% and 11%, respectively). Among infants 60 or more days old, Streptococcus pneumoniae, nontyphoidal salmonella species, Haemophilus influenzae, and E. coli accounted for more than 70% of isolates. The minimal annual incidence of community-acquired bacteremia was estimated at 1,457 cases per 100,000 children among infants under 1 year old, 1,080 among children under 2 years old, and 505 among children under 5 years old. Of all in-hospital deaths, 26% were in children with community-acquired bacteremia. Of 308 deaths in children with bacteremia, 103 (33.4%) occurred on the day of admission and 217 (70.5%) occurred within 2 days. Berkley et al. (2005) concluded that community-acquired bacteremia is a major cause of death among children at a rural sub-Saharan hospital. Mapping Susceptibility to bacteremia-2 (BACTS2) is caused by variation in the CISH gene (602441), which Uchida et al. (1997) mapped to chromosome 3p21.3 by FISH. Molecular Genetics Khor et al. (2010) used a case-control design to test for an association between polymorphisms in CISH (602441) and susceptibility to major infectious diseases, including bacteremia, tuberculosis (607948), and severe malaria (611162), in blood samples from 8,402 persons from Gambia, Hong Kong, Kenya, Malawi, and Vietnam. The study included 770 Kenyan children with bacteremia reported by Berkley et al. (2005). Khor et al. (2010) observed associations between variant alleles of multiple CISH polymorphisms and increased susceptibility to each infectious disease in each of the study populations. When all 5 SNPs, at positions -639, -292 (rs414171; 602441.0001), -163 (rs6768330), +1320 (rs2239751), and +3415 (rs622502), within the CISH-associated locus were considered together in a multiple-SNP score, Khor et al. (2010) found an association between CISH genetic variants and susceptibility to bacteremia, malaria, and tuberculosis (P = 3.8 x 10(-11) for all comparisons), and with -292 accounting for most of the association signal (P = 4.58 x 10(-7)). Peripheral blood mononuclear cells (PBMCs) obtained from adult subjects carrying the -292 variant, as compared with wildtype cells, showed a muted response to the stimulation of interleukin-2 (IL2; 147680) production, i.e., 25 to 40% less CISH expression. Khor et al. (2010) found that the overall risk of one of these infectious diseases was increased by at least 18% among persons carrying the variant CISH alleles. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	BACTEREMIA, SUSCEPTIBILITY TO, 2	c3280647	3,950	omim	https://www.omim.org/entry/614383	2019-09-22T15:55:26	{"omim": ["614383"]}
A number sign (#) is used with this entry because mutations in several genes may underlie susceptibility to uveal melanoma. Susceptibility loci have been mapped to chromosome 3q (UVM1; 606660) and chromosome 3p (UVM2; 606661). See also 614327 for a tumor predisposition syndrome that may include the development of uveal melanoma and is caused by germline mutation in the BAP1 gene (603089) on chromosome 3p21. Clinical Features Uveal melanoma is the most common primary intraocular malignancy. Canning and Hungerford (1988) found reports of 12 families with adequate documentation of the occurrence of uveal melanomas in 2 or more members. They described 2 more families, each with 2 affected members: a brother and sister who presented at ages 69 and 63 years, respectively, and a mother and son who presented at ages 33 and 20, respectively. Young et al. (1994) reported 11 families in which 2 or more members had uveal melanoma. The median age at diagnosis was 56.5 years, similar to the median age at diagnosis of the other patients treated at their institution. Of the 24 affected persons, 13 were male and 11 were female. In a review of medical charts of 4,500 patients with uveal melanoma, Singh et al. (1996) found 56 patients in 27 families with a family history. The uveal melanoma was unilateral in all 56 familial cases. In 17 cases (63%), the second affected relative was a first-degree relative; second-degree relatives accounted for 22% and third-degree relatives for 15%. In 25 families (93%), only 2 members were affected, and in 2 families (7%), 3 members had uveal melanoma. Patients with familial uveal melanoma were 4 times as likely to have a second primary malignant neoplasm than persons in the general population; however, unaffected relatives of these patients were apparently not at higher risk of having another primary malignant neoplasm. The authors stated that the occurrence of familial uveal melanoma is rare, comprising only 0.6% of all uveal melanoma patients. Singh and Topham (2003) determined the incidence of primary uveal melanoma in the United States over a 25-year period (1973-1997). They found 2,493 cases of uveal melanoma, representing 2.9% of all recorded cases of melanoma. The mean age-adjusted incidence was 4.3 per million. Most cases (97.8%) occurred in the white population. There was a significant variation of incidence between genders (males, 4.9; females, 3.7). There was no significant variation of incidence by the geographic location of the registry. The mean age-adjusted incidence of uveal melanoma in the United States (4.3 per million) was similar to that reported from European countries. The age-adjusted incidence rate of uveal melanoma had remained stable for over the 25 years. Singh et al. (2000) reported a man who presented with choroidal melanoma at the age of 41 and his 68-year-old father who presented with the same condition 6 months after his son. Using principles of probability, they stated that the likelihood of familial occurrence of uveal melanoma was approximately 1 in 10 million. Li et al. (2000) reviewed 1,848 consecutive primary choroidal and/or ciliary body melanoma patients treated with proton beam irradiation. They concluded that patients with melanomas of presumed ciliary body origin are subject to a higher risk of death resulting from melanoma metastasis. Al-Jamal et al. (2003) reported that the mean of the 10 largest nucleoli (MLN) was an independent predictor of survival in patients with uveal melanoma, when adjusting in turn for the presence of epithelioid cells, loops and networks, and microvascular density (MVD). The authors concluded that MLN and microvascular loops and networks were unrelated, independent predictors of survival. MLN and MVD were found to be partially interrelated. Multivariate models that included MVD in addition to MLN fitted better with observed melanoma-specific survival than models that excluded MVD. Subretinal fluid is a strong risk factor for growth of choroidal melanocytic tumors. Espinoza et al. (2004) found that optical coherence tomography was useful in distinguishing active subretinal fluid from chronic retinal changes overlying a choroidal melanocytic tumor and might be of predictive value in identifying tumors that are likely to grow and require treatment. Toivonen et al. (2004) investigated the relationship between progression to hepatic metastasis and tumor-infiltrating macrophages and microcirculation attributes in uveal melanoma, a cancer that almost invariably disseminates hematogenously to the liver. The authors found that the hepatic metastases had a significantly lower grade of pigmentation, more frequent epithelioid cells, more intermediate and dendritic types of CD68 (153634)-immunopositive macrophages than round ones, and a higher MVD than the primary uveal melanomas that spawned the metastases. Patient survival after diagnosis of disseminated disease tended to be shorter if hepatic metastases had a high MVD. Shields et al. (2004) reported the clinical variation and natural course of optic disc melanocytoma in 115 patients. Although optic disc melanocytoma is generally considered to be a benign, stationary lesion, they found that it can produce several local complications, can cause visual loss, can grow slowly, and can, rarely, undergo malignant transformation into melanoma. Shields et al. (2004) concluded that patients with optic disc melanocytoma should undergo periodic ocular examination. Zografos et al. (2004) reviewed 37 cases of optic disc melanocytoma in European patients. Tumor growth was demonstrated in 6 of 9 patients followed for at least 6 years. In 2 cases, presumed malignant transformation required treatment. Zografos et al. (2004) concluded that the risk of melanocytoma progression, although sometimes occurring as much as several years after the initial diagnosis, justifies a cautious approach with long-term regular surveillance. Elner et al. (2004) reviewed the clinical and echographic characteristics of a chronic, inactive choroidal nevus and a malignant choroidal melanoma. They concluded that documented growth is not an unequivocal indicator of malignant transformation for small melanocytic tumors. Elner et al. (2004) stated that the Collaborative Ocular Melanoma Study Group (1990) reported histopathologic examination of 413 eyes with a clinical diagnosis of choroidal melanoma and a misdiagnosis rate of 0.48%. All of these melanomas had a height greater than 2.5 mm, and Elner et al. (2004) noted that with lesions less than 2 mm in height, it is more difficult to distinguish a nevus from a melanoma. Hadden and Damato (2003) reported the occurrence of 2 entirely separate choroidal melanomas in the same eye of 1 patient, a 30-year-old woman. The first developed in her left eye. It was successfully treated with proton beam radiotherapy. One year later, she developed a pigmented lesion on her right calf. Excision biopsy revealed melanoma-in-situ. Four years later, a small choroidal tumor was noted in her left eye and was presumed to be a nevus. It was observed for 1 year. Because of rapid growth, choroidal melanoma was diagnosed. This second choroidal melanoma was treated with a ruthenium plaque. Six years later, both tumors had continued to regress and the patient remained in good health. Only 19 cases of multifocal uveal melanoma had been reported previously. Hadden and Damato (2003) concluded that a second uveal melanoma in the same eye suggested a genetic predisposition. Smith et al. (2007) evaluated a kindred in which several members had both uveal and cutaneous (see 155600) melanomas. The proband and his mother had uveal melanoma, 3 cutaneous melanomas occurred between 2 sibs, and 2 other sibs had basal cell carcinomas. No germline mutations were detected in the melanoma-associated tumor suppressor genes p16(INK4A) (600160) and p14(ARF) (see 600160). Seven of 10 sibs had a history of cutaneous and/or ocular nevi. Of the 3 subjects without nevi, 2 had histories of eye or skin malignancies (1 uveal melanoma and 1 basal cell carcinoma). Three of the 10 sibs had relevant ocular findings (2 choroidal nevi and 1 uveal melanoma). Six were also found to be in the 'high-risk' classification for cutaneous malignancies. Smith et al. (2007) concluded that their results strengthened the association between uveal melanoma, atypical nevi, and cutaneous melanoma. Diagnosis Goto et al. (2001) reported that single photon emission computed tomography (SPECT) images using a radiopharmaceutical was both sensitive and specific for the diagnosis of uveal melanoma. Eight of 20 eyes showed high accumulation of the radiopharmaceutical in the late phase in the area corresponding to the uveal tumor, and the diagnosis of uveal melanoma was confirmed histologically in 7 enucleated eyes. The 12 patients with no accumulation were found to have iris nevus, choroidal nevus, or other intraocular or adnexal conditions, clinically or histologically. Clinical Management Singh et al. (2000) reported the occurrence of retinoblastoma and uveal melanoma in the same patient. The patient had had enucleation of her right eye at age 3.5 years for unilateral sporadic retinoblastoma. Fifty years later, in 1990, she developed a visual field defect in her remaining left eye and was diagnosed with choroidal nevus. Barrier photocoagulation was performed in 1995 to limit subretinal fluid leakage. Because of growth of the lesion, choroidal melanoma was diagnosed in 1997. Transpupillary thermotherapy enhanced with indocyanine green was performed in an attempt to treat the tumor without risk of visual loss in her 20/20 left eye. Because of continued tumor growth, iodine-125 radioactive plaque was applied. At the 1-year follow-up, the patient had a visual acuity of 20/40 and the tumor had regressed. The authors calculated the probability of occurrence of unilateral retinoblastoma followed by uveal melanoma in the remaining eye at 1:165 billion. The Collaborative Ocular Melanoma Study Group (2001) described metastatic disease status at death in patients with large choroidal melanoma. Of the 1,003 patients enrolled in the trial, 457 had died. Thus, estimated median survival from time of enrollment was 7.4 years. The authors determined disease status at time of death for 435 of 457 patients (95%). Sixty-two percent had histopathologically confirmed melanoma metastasis at the time of death. Metastasis was suspected in a further 21% on the basis of imaging or other tests but was not histopathologically confirmed. Common metastatic sites were liver (93%), lung (24%), and bone (16%). Multiple sites were identified in 87% of patients with metastasis. The likelihood of 3 or more sites increased more than 4-fold when autopsy results were available (6%). The authors also suggested guidelines for the evaluation of patients in clinical studies of choroidal melanoma. Gombos et al. (2004) found significant differences among ocular oncologists in North America and Europe in the use of techniques to screen for metastatic uveal melanoma. North American members (from the United States and Canada) of the Collaborative Ocular Melanoma Study (COMS) centers relied primarily upon liver function tests and chest x-rays. The majority of European centers used liver ultrasonography. The authors urged ocular oncologists to design a cost-effective screening protocol for patients with uveal melanoma and to implement it uniformly. Shields et al. (2002) evaluated tumor control and treatment complications following plaque radiotherapy combined with transpupillary thermotherapy for 270 consecutive choroidal melanomas. Prior to treatment, the median base of the tumor was 11 mm (range 4-21 mm) and the median thickness was 4 mm (range 2-9 mm). All patients received plaque radiotherapy (median dose was 9000 rad to the tumor apex). Transpupillary thermotherapy (median dose 700 mW) was applied in 3 sessions beginning at plaque removal and continuing at 4-month intervals. At 5 years, treatment-related complications included maculopathy in 18% of patients, papillopathy in 38%, macular retinal vascular obstruction in 18%, vitreous hemorrhage in 18%, rhegmatogenous retinal detachment in 2%, cataract in 6%, and neovascular glaucoma in 7%. Enucleation for radiation complications was necessary in 3 cases (1%). The authors concluded that their protocol provided excellent tumor control with only 3% recurrence at 5 years' follow-up. Li et al. (2003) compared various methods of modeling the relationship between tumor dimension and metastatic death. They analyzed 1,204 consecutive patients with primary choroidal melanoma treated with proton beam irradiation. They found that tumor basal area was a better prognostic indicator than largest tumor diameter or tumor volume in the prediction of metastatic death after proton beam irradiation for uveal melanoma. Shields et al. (2002) presented the results of primary transpupillary thermotherapy in 256 patients with newly diagnosed small choroidal melanomas. After a mean of 3 treatment sessions, complete tumor control without recurrence was found in 91% of patients, with recurrence in 9%. Mean time to recurrence was 22 months. Tumor-related mortality occurred in 1% of patients. The authors concluded that transpupillary thermotherapy is an effective treatment for certain small choroidal melanomas and that appropriate tumor selection is critical to successful treatment. They cautioned that patients with tumors abutting or overhanging the optic disc, or those requiring more than 3 sessions for tumor control are more likely to develop recurrence. They also observed that transpupillary thermotherapy can damage the retina, leading to visual loss shortly after treatment. Krause et al. (2003) evaluated an infrared laser in the destruction of pigmented choroidal melanomas implanted in the subchoroidal space of rabbits. Twenty animals received a single treatment of focused 1047-nm light. The rate of complete tumor eradication was 91% in 10 of 11 animals receiving a dosage of 125 J/cm2. Continuous tumor growth was observed in all animals treated with collimated radiation and in untreated controls. Their data suggested that a single treatment with a focused, raster-scanned beam of 1047 nm might play a role in the destruction of pigmented choroidal melanomas. Singh et al. (2003) reported clinicopathologic correlations in 10 eyes that required enucleation after transpupillary thermotherapy for choroidal melanoma. Indications for enucleation included recurrence in 5 of 10, progression in 3 of 10, retinal detachment in 1 of 10, and neovascular glaucoma in 1 of 10. Interval between transpupillary thermotherapy and enucleation ranged from 6 to 70 months (mean 19.4 months). Despite satisfactory ophthalmoscopic evidence of regression, intrascleral extension occurred in some patients. The authors recommended routine B-scan ultrasonography to detect extrascleral extension in patients with choroidal melanoma. Dithmar et al. (2000) showed the usefulness of recombinant alpha-interferon (see 147562) for decreasing hepatic metastases from intraocular melanoma in a murine model. The authors concluded that adjuvant recombinant IFN alfa-2b treatment given before or at the time of enucleation might be a treatment option for patients with uveal melanoma with high-risk factors for developing metastatic disease. Kiratli and Bilgic (2001) reported that, although clinically detectable calcification in choroidal melanomas is extremely rare, progressive calcification as well as tumor regression in a posterior uveal melanoma may occur after treatment with infrared diode laser transpupillary thermotherapy. Singh et al. (2001) reported a 49-year-old patient who, 15 years after brachytherapy for left choroidal melanoma with excellent regression, developed a metastatic melanoma to the contralateral choroid as the first sign of metastasis. Systemic evaluation disclosed multiple metastases confined to the liver. The authors concluded that metastasis to the contralateral choroid may be the first sign of metastasis from choroidal melanoma. Hadden et al. (2004) reviewed the histopathology of eyes enucleated after endoresection of choroidal melanoma. As with other treatments conserving the eye, these authors stressed that enucleation should be performed if adequate ocular examination is no longer possible, and that follow-up should be lifelong. Kaiserman et al. (2004) evaluated trends in liver function tests (LFTs) before detection of liver metastases from uveal melanoma. At the time of diagnosis of liver metastases by imaging, 50% of patients had at least 1 abnormal LFT, compared with only 5% of the control group. Based on likelihood ratios, alkaline phosphatase and lactate dehydrogenase levels were the most predictive tests. The authors concluded that monitoring the changes in selected LFTs, even within normal limits, could help predict metastatic uveal melanoma. Primary malignant melanoma of the choroid and ciliary body has traditionally been treated without histologic staging, using purely clinical indicators. The presence of extravascular matrix patterns (EMPs) in histologic sections of uveal melanoma is an independent indicator of metastatic risk (Folberg et al., 1993). Coleman et al. (2004) presented evidence suggesting that ultrasound can be used to detect noninvasively the presence of clinically significant prognostic features of uveal melanoma related to EMP patterns, and for patient stratification to different treatment modalities based on assignment to high- or low-risk groups. The Collaborative Ocular Melanoma Study Group (2004) reported that at 10-year follow-up, no survival advantage was attributable to pre-enucleation radiation for large choroidal melanomas. They concluded that mortality rates by baseline characteristics should facilitate counseling of patients who have large choroidal melanoma and no evidence of metastasis or another malignancy at diagnosis. Sisley et al. (2011) reviewed the background of GNAQ mutations in uveal melanoma and discussed them as a therapeutic target. Biochemical Features Endocrine influence on cutaneous and uveal melanomas has been a topic of interest since Pack and Scharnagel (1951) reported that the prognosis for cutaneous melanoma is worse in pregnant women. Grostern et al. (2001) evaluated choroid melanomas in enucleated eyes for the presence of estrogen receptor-1 (ESR1; 133430). No tumors showed immunohistochemical evidence of ESR1. All-Ericsson et al. (2002) investigated the expression of insulin-like growth factor I receptor (IGF1R; 147370), focusing on its role in cell growth in uveal melanoma. Their data suggested a significant association between high IGF1R expression and death due to metastatic disease. Because IGF1R is produced mainly in the liver, the preferential site for uveal melanoma metastases, these results pointed to the possibility of interfering therapeutically with IGF1R in uveal melanoma that appears to follow an aggressive clinical course. Apte et al. (2001) assayed 7 uveal melanoma cell lines for their ability to produce angiostatin (173350) in vitro. Three cell lines generated 38-Kd angiostatin molecules that significantly inhibited bovine endothelial cell proliferation in vitro. Enucleation of eyes containing angiostatin-producing cell lines exacerbated the metastatic potential of the uveal melanomas. In contrast, enucleation of eyes containing a nonangiostatin-producing cell line had no significant effect on liver metastasis. The authors concluded that, in some circumstances, enucleation of a melanoma-containing eye might unwittingly exacerbate the metastatic potential of uveal melanoma. Ardjomand et al. (2003) investigated the distribution of somatostatin receptor subtypes 2 (SSTR2; 182452), 3 (SSTR3; 182453), and 5 (SSTR5; 182455) in uveal melanomas and their diagnostic and possible therapeutic value. All 25 uveal melanomas studied were positive for SSTR2: SSTR2A was expressed in 15 of 25; SSTR2B in 23 of 25; SSTR3 in 7 of 25; and SSTR5 in 13 of 25. A Kaplan-Meier survival curve showed a significantly better ad vitam prognosis for patients with tumors expressing high levels of SSTR2. Because a melanoma cell proliferation assay showed an inhibitory effect of up to 36% +/- 6% using octreotide or vapreotide, somatostatin analogs might be beneficial in the treatment of patients with ocular melanomas. Clarijs et al. (2003) stated that, in both primary uveal and cutaneous melanoma, 9 different patterns of extracellular matrix deposition have been identified by conventional periodic acid-Schiff (PAS) staining, and these patterns appear to be of prognostic significance. In particular, the presence of PAS-positive arcs, loops, and network patterns has been associated with poor survival. Along with PAS-positive patterns, numerous macrophages are present, and their recruitment into tumor tissue is mediated by chemotactic cytokines. Clarijs et al. (2003) showed that, in uveal melanoma, macrophages accumulate at sites of endothelial monocyte-activating polypeptide-2 (EMAP2; 603605) expression. They hypothesized that the chemotaxis process is facilitated by EMAP2-dependent expression of ICAM1 (147840) on vascular endothelial cells and concomitantly leads to localized vascular damage, as indicated by release of von Willebrand factor (VWF; 613160). Klisovic et al. (2003) reported that histone deacetylase inhibitors (HDACIs) such as depsipeptide inhibited primary and metastatic uveal melanoma cell growth in vitro. The apoptosis they observed was probably mediated through the Fas/FasL (134637, 134638) signaling pathway rather than via Bcl2 (151430). Reiniger et al. (2007) evaluated osteopontin (OPN; 166490) as a potential marker for screening and detection of metastatic uveal melanoma. Mean plasma concentration of OPN in 8 patients with uveal melanoma without metastasis was 46.8 ng/ml. Increased median levels of OPN of 170.7 ng/ml were seen in 8 patients with proven metastatic disease. In healthy control subjects, median plasma OPN concentration was 54.6 ng/ml. Reiniger et al. (2007) suggested that OPN is a promising tumor marker. Because of the potential immunogenicity of the melanocortin-1 receptor (MC1R; 155555), Lopez et al. (2007) evaluated its expression in uveal melanoma. Their results demonstrated that MC1R was expressed by uveal melanoma to a significantly greater extent than other melanoma markers. MC1R was found in 95% of melanoma tissues tested, including 1 liver metastasis. Even though MC1R was mainly located intracellularly, its cell surface expression could be promoted by cytokines, such as interferon-gamma (147570) and tumor necrosis factor-alpha (191160). The data supported MC1R as a new marker for the diagnosis of uveal melanoma and as a putative therapeutic target. Other Features Hurks et al. (2001) assayed 11 human uveal melanoma cell lines and 17 primary uveal melanomas for expression of HLA-G (142871), a nonclassical HLA class I molecule that is a critical mediator in the inhibition of natural killer (NK) cell-mediated cytolysis. Because none of the cell lines and none of the primary melanomas expressed HLA-G, the authors concluded that it is unlikely that HLA-G plays a role, direct or indirect, in the modulation of cellular immunity against uveal melanoma tumors. Cytogenetics In 19 patients with uveal melanoma, Mukai and Dryja (1985, 1986) sought evidence of homozygosity or hemizygosity for DNA polymorphisms that were heterozygous in the host. The rationale follows that which has been successful in the study of retinoblastoma and Wilms tumor. They found that 2 of the 15 informative patients had, in their tumors, lost alleles at loci on chromosome 2. Using DNA markers, Prescher et al. (1992) found loss of chromosome 3 alleles and multiplication of 8q alleles in uveal melanoma. Cytogenetic analysis had previously shown monosomy of chromosome 3 and multiplication of chromosome 8q material as nonrandom chromosomal aberrations. Horsthemke et al. (1992) interpreted the findings as indicating that a tumor suppressor gene on chromosome 3 and an oncogene on chromosome 8 are involved in the formation or progression of uveal melanoma. In 4 of 10 posterior uveal melanomas, all derived from the ciliary body, Sisley et al. (1992) demonstrated monosomy 3 and i(8q). See also Prescher et al. (1994). Tschentscher et al. (2001) stated that monosomy 3, an unusual finding in most tumors, is present in approximately 50% of uveal melanomas and is significantly correlated with metastatic disease. To obtain positional information on putative tumor suppressor genes on chromosome 3, they investigated tumors from 333 patients by comparative genomic hybridization, microsatellite analysis, or conventional karyotype analysis. A partial deletion of the long arm was found in 8 tumors, and the smallest region of deletion overlap (SRO) spanned 3q24-q26. They found 6 tumors with a partial deletion of the short arm and defined a second SRO of about 2.5 Mb in 3p25. This SRO did not overlap with the von Hippel-Lindau disease gene (608537). These findings suggested a role for 2 tumor suppressor genes (see 606660 and 606661) in metastasizing uveal melanoma and may explain the loss of an entire chromosome 3 in these tumors. Molecular Genetics Hearle et al. (2003) screened 385 patients with uveal melanomas for germline mutations in the BRCA2 (600185), p16(INK4A)/p14(ARF) (600160), and p15 (600431) genes. Their findings suggested that fewer than 2% of uveal melanoma cases could be ascribed to germline mutations in BRCA2, p16/p14, or p15. The authors concluded that it is likely that mutations in other genes contribute to an inherited predisposition to uveal melanoma. ### Somatic Mutations Maat et al. (2008) noted that mutations in the genes that control call proliferation in cutaneous melanoma are generally uncommon in uveal melanoma. However, using the very sensitive pyrophosphorolysis-activated polymerization (PAP) assay to screen for mutations in exon 15 of the BRAF gene (164757) in 11 uveal melanoma cell lines and 45 primary uveal melanomas, Maat et al. (2008) identified mutations in 2 cell lines (V600E; 164757.0001) and 6 primary tumors. Direct sequencing of the exon 15 PCR product did not reveal the mutations found with the PAP assay, indicating a low frequency of the mutant allele in primary samples. Maat et al. (2008) concluded that the relative scarcity of the BRAF mutations excluded an elemental role for them in uveal melanoma. Van Raamsdonk et al. (2009) reported frequent somatic mutations in the heterotrimeric G protein alpha-subunit (GNAQ; 600998) in blue nevi (603670) (83%) and ocular melanoma of the uvea (46%). The mutations occurred exclusively in codon 209 in the Ras-like domain and resulted in constitutive activation, turning GNAQ into a dominant-acting oncogene. Van Raamsdonk et al. (2009) concluded that their results demonstrated an alternative route to MAP kinase activation in melanocytic neoplasia, providing new opportunities for therapeutic intervention. Populo et al. (2011) identified the GNAQ Q209 mutation in 36% of 22 enucleated uveal melanomas. No associations were found between the presence of the GNAQ mutation and prognostic parameters, the expression of ERK1/2 (MAPK3, 601795/MAPK1, 176948), phosphorylated ERK1/2, and cell cycle markers. Populo et al. (2011) suggested that GNAQ-mutated uveal melanomas do not exhibit a higher deregulation of proliferation or higher activation of the MAP kinase signaling pathway than uveal melanomas without GNAQ activation. Van Raamsdonk et al. (2010) identified somatic mutations affecting residue Q209 of the GNA11 gene (139313) in 7% of blue nevi, 32% of primary uveal melanomas, and 57% of uveal melanoma metastases. Mutations in the same codon (Q209) of the paralogous GNAQ gene were found in 55% of blue nevi, 45% of primary uveal melanomas, and 22% of uveal melanoma metastases. The sample group included a total of 713 melanocytic neoplasms. Sequencing of exon 4 of both these genes, affecting residue R183, in 453 melanocytic neoplasms showed a lower prevalence of mutations, in 2.1% of blue nevi and 4.9% of primary uveal melanomas. The mutations were mutually exclusive, except for a single tumor that carried mutations at both Q209 and R183 in GNA11. In total, 83% of all uveal melanomas examined had oncogenic mutations in either GNAQ or GNA11. Mice injected with cells transduced with the GNA11 Q209L mutation developed rapidly growing tumors and metastases, whereas injection with GNA11 R183C-transduced cells showed lesser potency. Western blot analysis of melanocytes transduced with GNA11 Q209L showed constitutive activation of the MAPK pathway. Although GNA11 mutations appeared to have a more potent effect on melanocytes than did GNAQ mutations, there was no difference in patient survival among those with GNA11 mutations compared to those with GNAQ mutations. Harbour et al. (2010) used exome capture coupled with massively parallel sequencing to search for metastasis-related mutations in highly metastatic uveal melanomas of the eye. Inactivating somatic mutations were identified in the gene encoding BRCA1-associated protein-1 (BAP1; 603089) on chromosome 3p21.1 in 26 of 31 (84%) metastasizing tumors, including 15 mutations causing premature protein termination and 5 affecting its ubiquitin carboxyl-terminal hydrolase domain. One tumor harbored a frameshift mutation that was germline in origin, thus representing a susceptibility allele. Harbour et al. (2010) concluded that their findings implicated loss of BAP1 in uveal melanoma metastasis. Wiesner et al. (2011) found somatic mutations in the BAP1 gene in 13 (40%) of 33 uveal melanomas. All the uveal melanomas with BAP1 mutations also carried mutations at codon 209 in either GNAQ or GNA11. Harbour et al. (2013) described mutations occurring exclusively at codon 625 of the SF3B1 gene (605590) in low-grade uveal melanoma with good prognosis. Using exome sequencing, Martin et al. (2013) identified recurrent somatic mutations in EIF1AX (300186) and SF3B1, specifically occurring in uveal melanomas with disomy 3, which rarely metastasize. Targeted resequencing showed that 24 of 31 tumors with disomy 3 (77%) had mutations in either EIF1AX (15; 48%) or SF3B1 (9; 29%). Mutations were infrequent (2 of 35; 5.7%) in uveal melanomas with monosomy 3, which are associated with poor prognosis. Resequencing of 13 uveal melanomas with partial monosomy 3 identified 8 tumors with a mutation in either SF3B1 (7; 54%) or EIF1AX (1; 8%). All EIF1AX mutations caused in-frame changes affecting the N terminus of the protein, whereas 17 of 19 SF3B1 mutations encoded an alteration of arg625. Resequencing of 10 uveal melanomas with disomy 3 that developed metastases identified SF3B1 mutations in 3 tumors, none of which targeted arg625. Animal Model Murine uveal melanoma cells express have been found to secrete Vegf both locally and at distant sites of metastases, and local VEGF secretion has been observed in human uveal melanoma. VEGF secretion stimulates angiogenesis and can enhance metastatic potential. Crosby et al. (2011) evaluated Vegf expression in sera from mice inoculated with intraocular melanoma and correlated this with the number and location of hepatic metastases. Serum Vegf levels rose after inoculation of C56BL/6 mice eyes with B16LS9 cutaneous melanoma cells which, similar to human uveal melanoma, express high levels of c-met (164860) and metastasize to the liver. Beginning on day 14, there was a statistically significant increase in Vegf levels. Peak serum Vegf levels correlated with the total number of hepatic micrometastases (R = 0.444), and there was moderate correlation of peak Vegf serum levels with micrometastases in more hypoxic locations (R = 0.572). Vegf mRNA expression by micrometastases was highest in the most hypoxic regions of the hepatic lobule. Crosby et al. (2011) concluded that serum VEGF may be clinically useful as an early marker of micrometastasis or progression. Eyes \- Uveal melanoma Misc \- Most common primary intraocular malignancy \- Frequent loss of chromosome 3 material and additions of chromosome 8 Inheritance \- Autosomal dominant ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	MELANOMA, UVEAL	c0346388	3,951	omim	https://www.omim.org/entry/155720	2019-09-22T16:38:26	{"doid": ["6039"], "omim": ["155720"], "orphanet": ["39044"]}
Tumour of the glial cells of the brain or spine Glioma Glioma in the left parietal lobe (brain CT scan), WHO grade 2. SpecialtyOncology A glioma is a type of tumor that starts in the glial cells of the brain or the spine.[1] Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours.[2] ## Contents * 1 Signs and symptoms * 2 Causes * 2.1 Hereditary disorders * 2.2 Diet * 2.3 Radiation * 2.4 Infection with cytomegalovirus * 2.5 Other causes * 2.6 Inherited polymorphisms of the DNA repair genes * 3 Pathophysiology * 4 Diagnosis * 4.1 Classification * 4.1.1 By type of cell * 4.1.2 By grade * 4.1.3 By location * 5 Treatment * 5.1 Refractory disease * 5.2 Relative effectiveness * 6 Prognosis * 6.1 Low grade * 6.2 High grade * 6.3 Diffuse intrinsic pontine glioma * 6.4 IDH1 and IDH2-mutated glioma * 7 References * 8 External links ## Signs and symptoms[edit] Symptoms of gliomas depend on which part of the central nervous system is affected. A brain glioma can cause headaches, vomiting, seizures, and cranial nerve disorders as a result of increased intracranial pressure. A glioma of the optic nerve can cause visual loss. Spinal cord gliomas can cause pain, weakness, or numbness in the extremities. Gliomas do not usually metastasize by the bloodstream, but they can spread via the cerebrospinal fluid and cause "drop metastases" to the spinal cord.[medical citation needed] Complex visual hallucinations have been described as a symptom of low-grade glioma.[3] A child who has a subacute disorder of the central nervous system that produces cranial nerve abnormalities (especially of cranial nerve VII and the lower bulbar nerves), long-tract signs, unsteady gait secondary to spasticity, and some behavioral changes is most likely to have a pontine glioma.[4] ## Causes[edit] ### Hereditary disorders[edit] The exact causes of gliomas are not known. Hereditary disorders such as neurofibromatoses (type 1 and type 2) and tuberous sclerosis complex are known to predispose to their development.[5] Different oncogenes can cooperate in the development of gliomas.[6] ### Diet[edit] Some studies of diet and vitamin supplementation seem to indicate that dietary N-nitroso compounds might influence the risk of both childhood and adult brain tumors. Researchers have observed in some studies that brain tumor patients (or their mothers) have generally consumed more cured foods (also known as Curing) than control groups. Recently, Drs. Lee, Wrensch and others found that adults with glioma were more likely to consume diets high in cured foods and low in vitamin C-rich fruits and vegetables, and to consume diets high in nitrites and low in vitamin C. The effect was more pronounced in men than women. However, the pattern of increased risk with increased consumption of cured foods, and decreased risk with greater consumption of fruits, vegetables, and antioxidant vitamins is compatible with other cancer studies that show increased consumption of vegetables and possibly of fruits is associated with decreased cancer risk.[7] ### Radiation[edit] A link between gliomas and electromagnetic radiation from cell phones has not been conclusively proven.[8] It was considered possible,[9][10] though several large studies have found no conclusive evidence, as summarized by the NIH's National Cancer Institute review of the topic[11] and its numerous citations,[12] and the FCC.[13] However, further research is still being pursued to obtain more robust evidence and verify that there is no relationship (the NIH's National Institute of Environmental Health Sciences most recent press release discussed an ongoing study[14] showing mildly positive results,[15] although it appears there may have been issues with the control group dying prematurely[16]). ### Infection with cytomegalovirus[edit] Most glioblastomas are infected with cytomegalovirus, which speeds the development of tumors.[17][18][19] ### Other causes[edit] Though some studies have shown that farmers have higher rates of gliomas compared to the general population, exposure to farm animals or manure is not associated with glioma.[20][21] Later studies have not found an association between farming and gliomas; similar conflicting data concerns teachers and glioma. More consistent data show that architects, surveyors, retail workers, butchers, and engineers have higher rates of gliomas.[22] Most studies have found that pesticide exposure is probably not a cause of glioma, though a minority of studies have found an association.[22][23][24][25] ### Inherited polymorphisms of the DNA repair genes[edit] Germ-line (inherited) polymorphisms of the DNA repair genes ERCC1, ERCC2 (XPD) and XRCC1 increase the risk of glioma.[26] This indicates that altered or deficient repair of DNA damage contributes to the formation of gliomas. DNA damages are a likely major primary cause of progression to cancer in general.[citation needed] Excess DNA damages can give rise to mutations through translesion synthesis. Furthermore, incomplete DNA repair can give rise to epigenetic alterations or epimutations.[27][28] Such mutations and epimutations may provide a cell with a proliferative advantage which can then, by a process of natural selection, lead to progression to cancer.[citation needed] Epigenetic repression of DNA repair genes is often found in progression to sporadic glioblastoma. For instance, methylation of the DNA repair gene MGMT promoter was observed in 51% to 66% of glioblastoma specimens.[29][30] In addition, in some glioblastomas, the MGMT protein is deficient due to another type of epigenetic alteration. MGMT protein expression may also be reduced due to increased levels of a microRNA that inhibits the ability of the MGMT messenger RNA to produce the MGMT protein.[30] Zhang et al.[31] found, in the glioblastomas without methylated MGMT promoters, that the level of microRNA miR-181d is inversely correlated with protein expression of MGMT and that the direct target of miR-181d is the MGMT mRNA 3'UTR (the three prime untranslated region of MGMT messenger RNA). Epigenetic reductions in expression of another DNA repair protein, ERCC1, were found in an assortment of 32 gliomas.[32] For 17 of the 32 (53%) of the gliomas tested, ERCC1 protein expression was reduced or absent. In the case of 12 gliomas (37.5%) this reduction was due to methylation of the ERCC1 promoter. For the other 5 gliomas with reduced ERCC1 protein expression, the reduction could have been due to epigenetic alterations in microRNAs that affect ERCC1 expression.[citation needed] When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher than normal level, and such excess damages cause increased frequencies of mutation.[33][34][35] Mutations in gliomas frequently occur in either isocitrate dehydrogenase (IDH) 1 or 2 genes.[36] One of these mutations (mostly in IDH1) occurs in about 80% of low grade gliomas and secondary high-grade gliomas.[37] Wang et al.[38] pointed out that IDH1 and IDH2 mutant cells produce an excess metabolic intermediate, 2-hydroxyglutarate, which binds to catalytic sites in key enzymes that are important in altering histone and DNA promoter methylation. Thus, mutations in IDH1 and IDH2 generate a "DNA CpG island methylator phenotype or CIMP"[39][40] that causes promoter hypermethylation and concomitant silencing of tumor suppressor genes such as DNA repair genes MGMT and ERCC1. On the other hand, Cohen et al.[37] and Molenaar et al.[36] pointed out that mutations in IDH1 or IDH2 can cause increased oxidative stress. Increased oxidative damage to DNA could be mutagenic. This is supported by an increased number of DNA double-strand breaks in IDH1-mutated glioma cells.[41] Thus, IDH1 or IDH2 mutations act as driver mutations in glioma carcinogenesis, though it is not clear by which role they are primarily acting. A study, involving 51 patients with brain gliomas who had two or more biopsies over time, showed that mutation in the IDH1 gene occurred prior to the occurrence of a p53 mutation or a 1p/19q loss of heterozygosity, indicating that an IDH1 mutation is an early driver mutation.[42] ## Pathophysiology[edit] High-grade gliomas are highly vascular tumors and have a tendency to infiltrate diffusely.[43] They have extensive areas of necrosis and hypoxia. Often, tumor growth causes a breakdown of the blood–brain barrier in the vicinity of the tumor. As a rule, high-grade gliomas almost always grow back even after complete surgical excision, so are commonly called recurrent cancer of the brain.[medical citation needed] Conversely, low-grade gliomas grow slowly, often over many years, and can be followed without treatment unless they grow and cause symptoms.[medical citation needed] Several acquired (not inherited) genetic mutations have been found in gliomas. Tumor suppressor protein 53 (p53) is mutated early in the disease.[44] p53 is the "guardian of the genome", which, during DNA and cell duplication, makes sure the DNA is copied correctly and destroys the cell (apoptosis) if the DNA is mutated and cannot be fixed. When p53 itself is mutated, other mutations can survive. Phosphatase and tensin homolog (PTEN), another tumor suppressor gene, is itself lost or mutated. Epidermal growth factor receptor, a growth factor that normally stimulates cells to divide, is amplified and stimulates cells to divide too much. Together, these mutations lead to cells dividing uncontrollably, a hallmark of cancer. In 2009, mutations in IDH1 and IDH2 were found to be part of the mechanism and associated with a less favorable prognosis.[45] ## Diagnosis[edit] ### Classification[edit] Gliomas are classified by cell type, by grade, and by location. #### By type of cell[edit] Gliomas are named according to the specific type of cell with which they share histological features, but not necessarily from which they originate. The main types of gliomas are:[46] * Ependymomas: ependymal cells * Astrocytomas: astrocytes (glioblastoma multiforme is a malignant astrocytoma and the most common primary brain tumor among adults). * Oligodendrogliomas: oligodendrocytes * Brainstem glioma: develop in the brain stem * Optic nerve glioma: develop in or around the optic nerve * Mixed gliomas, such as oligoastrocytomas, contain cells from different types of glia #### By grade[edit] Gliomas are further categorized according to their grade, which is determined by pathologic evaluation of the tumor. The neuropathological evaluation and diagnostics of brain tumor specimens is performed according to WHO Classification of Tumours of the Central Nervous System.[47][48] Low-grade brain glioma in a 28-year-old male. (Taken on 10 July 2007) * Biologically benign gliomas [WHO grade I] are comparatively low risk and can be removed surgically depending on their location [43] * Low-grade gliomas [WHO grade II] are well-differentiated (not anaplastic); these tend to exhibit benign tendencies and portend a better prognosis for the patient. However, they have a uniform rate of recurrence and increase in grade over time so should be classified as malignant. * High-grade [WHO grades III–IV] gliomas are undifferentiated or anaplastic; these are malignant and carry a worse prognosis. Of numerous grading systems in use, the most common is the World Health Organization (WHO) grading system for astrocytoma, under which tumors are graded from I (least advanced disease—best prognosis) to IV (most advanced disease—worst prognosis). #### By location[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (October 2019) (Learn how and when to remove this template message) Gliomas can be classified according to whether they are above or below a membrane in the brain called the tentorium. The tentorium separates the cerebrum (above) from the cerebellum (below). * The supratentorial is above the tentorium, in the cerebrum, and mostly found in adults (70%). * The infratentorial is below the tentorium, in the cerebellum, and mostly found in children (70%). * The pontine tumors are located in the pons of the brainstem. The brainstem has three parts (pons, midbrain, and medulla); the pons controls critical functions such as breathing, making surgery on these extremely dangerous. ## Treatment[edit] Treatment for brain gliomas depends on the location, the cell type, and the grade of malignancy. Often, treatment is a combined approach, using surgery, radiation therapy, and chemotherapy. The radiation therapy is in the form of external beam radiation or the stereotactic approach using radiosurgery. Spinal cord tumors can be treated by surgery and radiation. Temozolomide is a chemotherapy drug which can be administered easily in an outpatient setting and is able to cross the blood–brain barrier effectively.[49] Treatment via immunotherapy may help some gliomas.[50][51] ### Refractory disease[edit] For recurrent high-grade glioblastoma, recent studies have taken advantage of angiogenic blockers such as bevacizumab in combination with conventional chemotherapy, with encouraging results.[52] ### Relative effectiveness[edit] A 2017 meta-analysis compared surgical resection versus biopsy as the initial surgical management option for a person with a low-grade glioma.[53] Results show the evidence is insufficient to make a reliable decision.[53] The relative effectiveness of surgical resection compared to biopsy for people with malignant glioma (high-grade) is unknown.[54] For high-grade gliomas, a 2003 meta-analysis compared radiotherapy with radiotherapy and chemotherapy. It showed a small but clear improvement from using chemotherapy with radiotherapy.[55] A 2019 meta-analysis suggested that for people with less aggressive gliomas, radiotherapy may increase the risk of long term neurocognitive side effects.[56] Whilst, evidence is uncertain on whether there are long term neurocognitive side effects associated with chemoradiotherapy.[56] Temozolomide is effective for treating Glioblastoma Multiforme (GBM) compared to radiotherapy alone.[49] A 2013 meta-analysis showed that Temozolomide prolongs survival and delays progression, but is associated with an increase in side effects such as blood complications, fatigue, and infection.[49] For people with recurrent GBM, when comparing temozolomide with chemotherapy, there may be an improvement in the time-to-progression and the person's quality of life, but no improvement in overall survival, with temozolomide treatment.[49] Evidence suggests that for people with recurrent high-grade gliomas who have not had chemotherapy before, there are similar survival and time-to-progression outcomes between treatment with temozolomide or the chemotherapy multidrug known as PCV (procarvazine, lomustine and vincristine).[57] A mutational analysis of 23 initial low-grade gliomas and recurrent tumors from the same patients has challenged the benefits and usage of Temozolomide. The study showed that when lower-grade brain tumors of patients are removed and patients are further treated with Temozolomide, 6 out of 10 times the recurrent tumors were more aggressive and acquired alternative and more mutations.[58] As one of the last authors, Costello, stated "They had a 20- to 50-fold increase in the number of mutations. A patient who received surgery alone who might have had 50 mutations in the initial tumor and 60 in the recurrence. But patients who received TMZ might have 2,000 mutations in the recurrence."[59] Further, new mutations were verified to carry known signatures of Temozolomide induced mutations. The research suggests that Temozolomide for the treatment of certain brain tumors should be thoroughly thought. Unjudicious usage of Temozolomide might lower the prognosis of the patients further, or increase their burden. Further understanding of the mechanisms of Temozolomide induced mutations and novel combination approaches could be promising.[medical citation needed] ## Prognosis[edit] This section needs to be updated. Please update this article to reflect recent events or newly available information. Last update: (see PMID 24711712 for a better source) (September 2014) Prognosis of gliomas is given in relation to what grade (as scored by the World Health Organization system) of tumour the patient presents with. Typically, any tumour presenting as above WHO grade I (i.e. a malignant tumour as opposed to a benign tumour) will have a prognosis resulting in eventual death, varying from years (WHO grade II/III) to months (WHO grade IV).[43][60] Prognosis can also be given based on cellular subtype, which may also impact prognosis. ### Low grade[edit] For low-grade tumors, the prognosis is somewhat more optimistic. Patients diagnosed with a low-grade glioma are 17 times as likely to die as matched patients in the general population.[61] The age-standardized 10-year relative survival rate was 47%.[61] One study reported that low-grade oligodendroglioma patients have a median survival of 11.6 years;[62] another reported a median survival of 16.7 years.[63] Unfortunately, approximately 70% of low-grade (WHO grade-II) will progress to high-grade tumours within 5–10 years [43] ### High grade[edit] This group comprises anaplastic astrocytomas and glioblastoma multiforme. Whereas the median overall survival of anaplastic (WHO grade III) gliomas is approximately 3 years, glioblastoma multiforme has a poor median overall survival of c. 15 months.[64] Postoperative conventional daily radiotherapy improves survival for adults with good functional well‐being and high grade glioma compared to no postoperative radiotherapy. Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy, particularly for individuals aged 60 and older with glioblastoma.[65] ### Diffuse intrinsic pontine glioma[edit] Main article: Diffuse intrinsic pontine glioma Diffuse intrinsic pontine glioma primarily affects children, usually between the ages of 5 and 7.[66] The median survival time with DIPG is under 12 months.[67] Surgery to attempt tumour removal is usually not possible or advisable for DIPG. By their very nature, these tumours invade diffusely throughout the brain stem, growing between normal nerve cells. Aggressive surgery would cause severe damage to neural structures vital for arm and leg movement, eye movement, swallowing, breathing, and even consciousness.[68][69][unreliable medical source?] Trials of drug candidates have been unsuccessful.[70] The disease is primarily treated with radiation therapy alone.[medical citation needed] ### IDH1 and IDH2-mutated glioma[edit] Patients with glioma carrying mutations in either IDH1 or IDH2 have a relatively favorable survival, compared with patients with glioma with wild-type IDH1/2 genes. In WHO grade III glioma, IDH1/2-mutated glioma have a median prognosis of ~3.5 years, whereas IDH1/2 wild-type glioma perform poor with a median overall survival of c. 1.5 years.[36] In glioblastoma, the difference is larger. There, IDH1/2 wild-type glioblastoma have a median overall survival of 1 year, whereas IDH1/2-mutated glioblastoma have a median overall survival of more than 3 years.[71] ## References[edit] 1. ^ Mamelak AN, Jacoby DB (March 2007). "Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601)". Expert Opinion on Drug Delivery. 4 (2): 175–86. doi:10.1517/17425247.4.2.175. PMID 17335414. 2. ^ Goodenberger ML, Jenkins RB (December 2012). "Genetics of adult glioma". Cancer Genetics. 205 (12): 613–21. doi:10.1016/j.cancergen.2012.10.009. PMID 23238284. 3. ^ Lim A, Weir P, O'Brien TJ, Kaye AH (January 2011). "Complex visual hallucinations as a presentation of temporal low-grade glioma". Journal of Clinical Neuroscience. 18 (1): 157–9. doi:10.1016/j.jocn.2010.07.112. PMID 20965734. 4. ^ PRETEST pediatrics p. 224 5. ^ Reuss D, von Deimling A (2009). "Hereditary tumor syndromes and gliomas". Recent Results in Cancer Research. Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer. Recent Results in Cancer Research. 171: 83–102. doi:10.1007/978-3-540-31206-2_5. ISBN 978-3-540-31205-5. PMID 19322539. 6. ^ Radner H, el-Shabrawi Y, Eibl RH, Brüstle O, Kenner L, Kleihues P, Wiestler OD (1993). "Tumor induction by ras and myc oncogenes in fetal and neonatal brain: modulating effects of developmental stage and retroviral dose". Acta Neuropathologica. 86 (5): 456–65. doi:10.1007/bf00228580. PMID 8310796. 7. ^ http://www.kallansklan.org/uploads/FactSheet-WhoGetsBTsv_20rev.pdf[full citation needed] 8. ^ Söderqvist F, Carlberg M, Hansson Mild K, Hardell L (December 2011). "Childhood brain tumour risk and its association with wireless phones: a commentary". Environmental Health. 10 (106): 106. doi:10.1186/1476-069X-10-106. PMC 3278351. PMID 22182218. 9. ^ Morgan LL, Kesari S, Davis DL (2014). "Why children absorb more microwave radiation than adults: The consequences". Journal of Microscopy and Ultrastructure. 4 (2): 197–204. doi:10.1016/j.jmau.2014.06.005. 10. ^ "IARC classifies radiofrequency electromagnetic fields as possibly carcinogenic to humans" (PDF) (Press release). IARC. 31 May 2011. 11. ^ "Cell Phones and Cancer Risk". National Cancer Institute. Retrieved 29 May 2016. 12. ^ "Cell Phones and Cancer Risk (References)". National Cancer Institute. Retrieved 29 May 2016. 13. ^ "Wireless Devices and Health Concerns". Federal Communications Commission (FCC). 26 May 2011. Retrieved 29 May 2016. 14. ^ "Media Telebriefing: NTP Cell Phone Radiofrequency Radiation Study: Partial Release of Findings". www.niehs.nih.gov (Press release). Retrieved 29 May 2016. 15. ^ Wyde M, Cesta M, Blystone C, et al. (1 January 2018). "Report of Partial findings from the National Toxicology Program Carcinogenesis Studies of Cell Phone Radiofrequency Radiation in Hsd: Sprague Dawley SD rats (Whole Body Exposure)". bioRxiv 10.1101/055699. 16. ^ Storrs C (27 May 2016). "Cell phone radiation increases cancers in rats, but should we worry?". CNN. Retrieved 29 May 2016. 17. ^ Michaelis M, Baumgarten P, Mittelbronn M, Driever PH, Doerr HW, Cinatl J (February 2011). "Oncomodulation by human cytomegalovirus: novel clinical findings open new roads". Medical Microbiology and Immunology. 200 (1): 1–5. doi:10.1007/s00430-010-0177-7. PMID 20967552. 18. ^ Barami K (July 2010). "Oncomodulatory mechanisms of human cytomegalovirus in gliomas". Journal of Clinical Neuroscience. 17 (7): 819–23. doi:10.1016/j.jocn.2009.10.040. PMID 20427188. 19. ^ Dziurzynski K, Chang SM, Heimberger AB, Kalejta RF, McGregor Dallas SR, Smit M, et al. (March 2012). HCMV and Gliomas Symposium. "Consensus on the role of human cytomegalovirus in glioblastoma". Neuro-Oncology. 14 (3): 246–55. doi:10.1093/neuonc/nor227. PMC 3280809. PMID 22319219. 20. ^ Efird JT, Davies SW, O'Neal WT, Anderson EJ (2014). "Animal viruses, bacteria, and cancer: a brief commentary". Frontiers in Public Health. 2: 14. doi:10.3389/fpubh.2014.00014. PMC 3923154. PMID 24592380. 21. ^ Ruder AM, Carreón T, Butler MA, Calvert GM, Davis-King KE, Waters MA, et al. (June 2009). "Exposure to farm crops, livestock, and farm tasks and risk of glioma: the Upper Midwest Health Study". American Journal of Epidemiology. 169 (12): 1479–91. doi:10.1093/aje/kwp075. PMID 19403843. 22. ^ a b Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, et al. (July 2014). "The epidemiology of glioma in adults: a "state of the science" review". Neuro-Oncology. 16 (7): 896–913. doi:10.1093/neuonc/nou087. PMC 4057143. PMID 24842956. 23. ^ "Women's Safety and Health Issues at Work: Job Area: Agriculture". National Institute for Occupational Safety and Health (NIOSH). Archived from the original on 22 August 2015. Retrieved 20 June 2015. 24. ^ Carreón T, Butler MA, Ruder AM, Waters MA, Davis-King KE, Calvert GM, et al. (May 2005). "Gliomas and farm pesticide exposure in women: the Upper Midwest Health Study". Environmental Health Perspectives. 113 (5): 546–51. doi:10.1289/ehp.7456. PMC 1257545. PMID 15866761. 25. ^ Yiin JH, Ruder AM, Stewart PA, Waters MA, Carreón T, Butler MA, et al. (June 2012). "The Upper Midwest Health Study: a case-control study of pesticide applicators and risk of glioma". Environmental Health. 11: 39. doi:10.1186/1476-069X-11-39. PMC 3406961. PMID 22691464. 26. ^ Adel Fahmideh M, Schwartzbaum J, Frumento P, Feychting M (June 2014). "Association between DNA repair gene polymorphisms and risk of glioma: a systematic review and meta-analysis". Neuro-Oncology. 16 (6): 807–14. doi:10.1093/neuonc/nou003. PMC 4022225. PMID 24500421. 27. ^ Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, et al. (July 2007). "DNA damage, homology-directed repair, and DNA methylation". PLOS Genetics. 3 (7): e110. doi:10.1371/journal.pgen.0030110. PMC 1913100. PMID 17616978. 28. ^ O'Hagan HM, Mohammad HP, Baylin SB (August 2008). "Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island". PLOS Genetics. 4 (8): e1000155. doi:10.1371/journal.pgen.1000155. PMC 2491723. PMID 18704159. 29. ^ Skiriute D, Vaitkiene P, Saferis V, Asmoniene V, Skauminas K, Deltuva VP, Tamasauskas A (June 2012). "MGMT, GATA6, CD81, DR4, and CASP8 gene promoter methylation in glioblastoma". BMC Cancer. 12: 218. doi:10.1186/1471-2407-12-218. PMC 3404983. PMID 22672670. 30. ^ a b Spiegl-Kreinecker S, Pirker C, Filipits M, Lötsch D, Buchroithner J, Pichler J, et al. (January 2010). "O6-Methylguanine DNA methyltransferase protein expression in tumor cells predicts outcome of temozolomide therapy in glioblastoma patients". Neuro-Oncology. 12 (1): 28–36. doi:10.1093/neuonc/nop003. PMC 2940563. PMID 20150365. 31. ^ Zhang W, Zhang J, Hoadley K, Kushwaha D, Ramakrishnan V, Li S, et al. (June 2012). "miR-181d: a predictive glioblastoma biomarker that downregulates MGMT expression". Neuro-Oncology. 14 (6): 712–9. doi:10.1093/neuonc/nos089. PMC 3367855. PMID 22570426. 32. ^ Chen HY, Shao CJ, Chen FR, Kwan AL, Chen ZP (April 2010). "Role of ERCC1 promoter hypermethylation in drug resistance to cisplatin in human gliomas". International Journal of Cancer. 126 (8): 1944–1954. doi:10.1002/ijc.24772. PMID 19626585. 33. ^ Narayanan L, Fritzell JA, Baker SM, Liskay RM, Glazer PM (April 1997). "Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2". Proceedings of the National Academy of Sciences of the United States of America. 94 (7): 3122–7. Bibcode:1997PNAS...94.3122N. doi:10.1073/pnas.94.7.3122. PMC 20332. PMID 9096356. 34. ^ Hegan DC, Narayanan L, Jirik FR, Edelmann W, Liskay RM, Glazer PM (December 2006). "Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6". Carcinogenesis. 27 (12): 2402–8. doi:10.1093/carcin/bgl079. PMC 2612936. PMID 16728433. 35. ^ Tutt AN, van Oostrom CT, Ross GM, van Steeg H, Ashworth A (March 2002). "Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation". EMBO Reports. 3 (3): 255–60. doi:10.1093/embo-reports/kvf037. PMC 1084010. PMID 11850397. 36. ^ a b c Molenaar RJ, Radivoyevitch T, Maciejewski JP, van Noorden CJ, Bleeker FE (December 2014). "The driver and passenger effects of isocitrate dehydrogenase 1 and 2 mutations in oncogenesis and survival prolongation". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1846 (2): 326–41. doi:10.1016/j.bbcan.2014.05.004. PMID 24880135. 37. ^ a b Cohen AL, Holmen SL, Colman H (May 2013). "IDH1 and IDH2 mutations in gliomas". Current Neurology and Neuroscience Reports. 13 (5): 345. doi:10.1007/s11910-013-0345-4. PMC 4109985. PMID 23532369. 38. ^ Wang P, Dong Q, Zhang C, Kuan PF, Liu Y, Jeck WR, et al. (June 2013). "Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas". Oncogene. 32 (25): 3091–100. doi:10.1038/onc.2012.315. PMC 3500578. PMID 22824796. 39. ^ Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP (July 1999). "CpG island methylator phenotype in colorectal cancer". Proceedings of the National Academy of Sciences of the United States of America. 96 (15): 8681–6. Bibcode:1999PNAS...96.8681T. doi:10.1073/pnas.96.15.8681. PMC 17576. PMID 10411935. 40. ^ Nazemalhosseini Mojarad E, Kuppen PJ, Aghdaei HA, Zali MR (2013). "The CpG island methylator phenotype (CIMP) in colorectal cancer". Gastroenterology and Hepatology from Bed to Bench. 6 (3): 120–8. PMC 4017514. PMID 24834258. 41. ^ Molenaar RJ, Botman D, Smits MA, Hira VV, van Lith SA, Stap J, et al. (November 2015). "Radioprotection of IDH1-Mutated Cancer Cells by the IDH1-Mutant Inhibitor AGI-5198". Cancer Research. 75 (22): 4790–802. doi:10.1158/0008-5472.CAN-14-3603. PMID 26363012. 42. ^ Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (April 2009). "IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas". The American Journal of Pathology. 174 (4): 1149–53. doi:10.2353/ajpath.2009.080958. PMC 2671348. PMID 19246647. 43. ^ a b c d Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK, DePinho RA (June 2001). "Malignant glioma: genetics and biology of a grave matter". Genes & Development. 15 (11): 1311–33. doi:10.1101/gad.891601. PMID 11390353. 44. ^ von Deimling A, Eibl RH, Ohgaki H, Louis DN, von Ammon K, Petersen I, et al. (May 1992). "p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma". Cancer Research. 52 (10): 2987–90. PMID 1349850. 45. ^ Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, et al. (February 2009). "IDH1 and IDH2 mutations in gliomas". The New England Journal of Medicine. 360 (8): 765–73. doi:10.1056/NEJMoa0808710. PMC 2820383. PMID 19228619. 46. ^ "Gliomas". Johns Hopkins Medicine Health Library. Retrieved 19 April 2017. 47. ^ Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. (June 2016). "The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary". Acta Neuropathologica. 131 (6): 803–20. doi:10.1007/s00401-016-1545-1. PMID 27157931. 48. ^ Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, eds. (2016). WHO classification of tumours of the central nervous system. World Health Organization (Revised 4th ed.). Lyon: International Agency for Research on Cancer. ISBN 9789283244929. OCLC 951745876.[page needed] 49. ^ a b c d Hart MG, Garside R, Rogers G, Stein K, Grant R (April 2013). "Temozolomide for high grade glioma". The Cochrane Database of Systematic Reviews. 4 (4): CD007415. doi:10.1002/14651858.CD007415.pub2. PMC 6457743. PMID 23633341. 50. ^ Platten M, Bunse L, Wick W, Bunse T (October 2016). "Concepts in glioma immunotherapy". Cancer Immunology, Immunotherapy. 65 (10): 1269–75. doi:10.1007/s00262-016-1874-x. PMID 27460064. 51. ^ Patel MA, Pardoll DM (July 2015). "Concepts of immunotherapy for glioma". Journal of Neuro-Oncology. 123 (3): 323–30. doi:10.1007/s11060-015-1810-5. PMC 4498978. PMID 26070552. 52. ^ Wong ET, Brem S (October 2007). "Taming glioblastoma: targeting angiogenesis". Journal of Clinical Oncology. 25 (30): 4705–6. doi:10.1200/JCO.2007.13.1037. PMID 17947716. S2CID 6164155. 53. ^ a b Jiang B, Chaichana K, Veeravagu A, Chang SD, Black KL, Patil CG (April 2017). "Biopsy versus resection for the management of low-grade gliomas". The Cochrane Database of Systematic Reviews. 4: CD009319. doi:10.1002/14651858.CD009319.pub3. PMC 6478300. PMID 28447767. 54. ^ Hart MG, Grant GR, Solyom EF, Grant R (June 2019). "Biopsy versus resection for high-grade glioma". The Cochrane Database of Systematic Reviews. 6: CD002034. doi:10.1002/14651858.CD002034.pub2. PMC 6553559. PMID 31169915. 55. ^ Glioma Meta-Analysis Trialists (GMT) Group; et al. (Glioma Meta-analysis Trialists Group) (2002). Stewart, Lesley (ed.). "Chemotherapy for high-grade glioma". The Cochrane Database of Systematic Reviews (4): CD003913. doi:10.1002/14651858.CD003913. PMID 12519620. 56. ^ a b Lawrie TA, Gillespie D, Dowswell T, Evans J, Erridge S, Vale L, et al. (August 2019). "Long-term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma". The Cochrane Database of Systematic Reviews. 8: CD013047. doi:10.1002/14651858.cd013047.pub2. PMC 6699681. PMID 31425631. 57. ^ Parasramka S, Talari G, Rosenfeld M, Guo J, Villano JL (July 2017). "Procarbazine, lomustine and vincristine for recurrent high-grade glioma". The Cochrane Database of Systematic Reviews. 7: CD011773. doi:10.1002/14651858.cd011773.pub2. PMC 6483418. PMID 28744879. 58. ^ Johnson BE, Mazor T, Hong C, Barnes M, Aihara K, McLean CY, et al. (January 2014). "Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma". Science. 343 (6167): 189–193. Bibcode:2014Sci...343..189J. doi:10.1126/science.1239947. PMC 3998672. PMID 24336570. 59. ^ "Recurrent Brain Cancers Follow Distinctive Genetic Paths". University of California Santa Cruz. University of California San Francisco. Retrieved 17 June 2015. 60. ^ Sanai N, Chang S, Berger MS (November 2011). "Low-grade gliomas in adults". Journal of Neurosurgery. 115 (5): 948–65. doi:10.3171/2011.7.JNS101238. PMID 22043865. 61. ^ a b Smoll NR, Gautschi OP, Schatlo B, Schaller K, Weber DC (August 2012). "Relative survival of patients with supratentorial low-grade gliomas". Neuro-Oncology. 14 (8): 1062–9. doi:10.1093/neuonc/nos144. PMC 3408266. PMID 22773277. 62. ^ Ohgaki H, Kleihues P (June 2005). "Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas". Journal of Neuropathology and Experimental Neurology. 64 (6): 479–89. doi:10.1093/jnen/64.6.479. PMID 15977639. 63. ^ Olson JD, Riedel E, DeAngelis LM (April 2000). "Long-term outcome of low-grade oligodendroglioma and mixed glioma". Neurology. 54 (7): 1442–8. doi:10.1212/WNL.54.7.1442. PMID 10751254. 64. ^ Bleeker FE, Molenaar RJ, Leenstra S (May 2012). "Recent advances in the molecular understanding of glioblastoma". Journal of Neuro-Oncology. 108 (1): 11–27. doi:10.1007/s11060-011-0793-0. PMC 3337398. PMID 22270850. 65. ^ Khan L, Soliman H, Sahgal A, Perry J, Xu W, Tsao MN (May 2020). "External beam radiation dose escalation for high grade glioma". Cochrane Database of Systematic Reviews. 5: CD011475. doi:10.1002/14651858.CD011475.pub3. PMID 32437039. 66. ^ "Patients & Families: Basic Facts". DIPG Registry. Archived from the original on 2 May 2014. Retrieved 1 May 2014. 67. ^ Kebudi R, Cakir FB (October 2013). "Management of diffuse pontine gliomas in children: recent developments". Paediatric Drugs. 15 (5): 351–62. doi:10.1007/s40272-013-0033-5. PMID 23719782. 68. ^ Fisher PG, Breiter SN, Carson BS, Wharam MD, Williams JA, Weingart JD, et al. (October 2000). "A clinicopathologic reappraisal of brain stem tumor classification. Identification of pilocystic astrocytoma and fibrillary astrocytoma as distinct entities". Cancer. 89 (7): 1569–76. doi:10.1002/1097-0142(20001001)89:7<1569::aid-cncr22>3.0.co;2-0. PMID 11013373. 69. ^ Donaldson SS, Laningham F, Fisher PG (March 2006). "Advances toward an understanding of brainstem gliomas". Journal of Clinical Oncology. 24 (8): 1266–72. doi:10.1200/jco.2005.04.6599. PMID 16525181. 70. ^ Jansen MH, van Vuurden DG, Vandertop WP, Kaspers GJ (February 2012). "Diffuse intrinsic pontine gliomas: a systematic update on clinical trials and biology". Cancer Treatment Reviews. 38 (1): 27–35. doi:10.1016/j.ctrv.2011.06.007. PMID 21764221. 71. ^ Molenaar RJ, Verbaan D, Lamba S, Zanon C, Jeuken JW, Boots-Sprenger SH, et al. (September 2014). "The combination of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone". Neuro-Oncology. 16 (9): 1263–73. doi:10.1093/neuonc/nou005. PMC 4136888. PMID 24510240. ## External links[edit] Classification D * ICD-10: C71 * ICD-9-CM: 191 * ICD-O: M9380/3-9460/3 * MeSH: D005910 * DiseasesDB: 31468 * Glioma at the Human Protein Atlas * American Brain Tumor Association: Malignant Gliomas * Brain and Spinal Tumors: Hope Through Research (National Institute of Neurological Disorders and Stroke) * WHO Classification of Glioma * Glioma Images MedPix Database * v * t * e Tumours of the nervous system Endocrine Sellar: * Craniopharyngioma * Pituicytoma Other: * Pinealoma CNS Neuroepithelial (brain tumors, spinal tumors) Glioma Astrocyte * Astrocytoma * Pilocytic astrocytoma * Pleomorphic xanthoastrocytoma * Subependymal giant cell astrocytoma * Fibrillary astrocytoma * Anaplastic astrocytoma * Glioblastoma multiforme Oligodendrocyte * Oligodendroglioma * Anaplastic oligodendroglioma Ependyma * Ependymoma * Subependymoma Choroid plexus * Choroid plexus tumor * Choroid plexus papilloma * Choroid plexus carcinoma Multiple/unknown * Oligoastrocytoma * Gliomatosis cerebri * Gliosarcoma Mature neuron * Ganglioneuroma: Ganglioglioma * Retinoblastoma * Neurocytoma * Dysembryoplastic neuroepithelial tumour * Lhermitte–Duclos disease PNET * Neuroblastoma * Esthesioneuroblastoma * Ganglioneuroblastoma * Medulloblastoma * Atypical teratoid rhabdoid tumor Primitive * Medulloepithelioma Meninges * Meningioma * Hemangiopericytoma Hematopoietic * Primary central nervous system lymphoma PNS: * Nerve sheath tumor * Cranial and paraspinal nerves * Neurofibroma * Neurofibromatosis * Neurilemmoma/Schwannoma * Acoustic neuroma * Malignant peripheral nerve sheath tumor Other * WHO classification of the tumors of the central nervous system Note: Not all brain tumors are of nervous tissue, and not all nervous tissue tumors are in the brain (see brain metastasis). * Medicine portal [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Glioma	c0017638	3,952	wikipedia	https://en.wikipedia.org/wiki/Glioma	2021-01-18T19:01:32	{"gard": ["6513"], "mesh": ["D005910"], "umls": ["C0017638", "C0555198"], "orphanet": ["182067"], "wikidata": ["Q1365309"]}
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (May 2013) Rhabdomyoma is a benign mesenchymal tumor of skeletal muscle, separated into two major categories based on site: Cardiac and extracardiac. They are further separated by histology: fetal (myxoid and cellular), juvenile (intermediate), and adult types. Genital types are recognized, but are often part of either the fetal or juvenile types. The fetal type is thought to recapitulate immature skeletal muscle at about week six to ten of gestational development. ## Contents * 1 Signs and symptoms * 2 Pathophysiology * 2.1 Gross pathology * 2.2 Microscopic pathology * 3 Diagnosis * 3.1 Ancillary testing * 3.2 Differential diagnosis * 4 Management * 5 Epidemiology * 6 References ## Signs and symptoms[edit] Most fetal rhabdomyomas are tumors that develop in the head and neck or in the genital region.[1] There are a number of cases which have been seen in association with Gorlin syndrome.[2][3] However, cardiac myxomas are known to be associated with tuberous sclerosis. ## Pathophysiology[edit] ### Gross pathology[edit] The tumor may be seen within the subcutaneous tissues (below the skin),[4] mucosal surfaces or in soft tissue. Within the head and neck, the posterior ear region, skin of the face, and the tongue are the most commonly affected sites (about a 2:1 ratio of soft tissue to mucosa).[5][6] The tumors are well defined, non-specific usually solitary masses, but when seen in the head and neck (or genital region), they may be polypoid. Tumors range in dimension from a few millimeters up to 12.5 cm, with a mean of about 3.0 cm. Although there are isolated case reports, multifocality is very rare. ### Microscopic pathology[edit] A hematoxylin and eosin stained image (high power) of the short spindle cells of a fetal rhabdomyoma. Fetal rhabdomyoma are separated into two histologic types: Myxoid and cellular.[7][8] However, irrespective of histologic type, these tumors almost never show necrosis or increased mitoses. However, a cambium layer, abnormal mitoses and nuclear pleomorphism is not seen. Cellular fetal rhabdomyomas are composed of bland, primitive spindled cells. The spindle cells are haphazardly arranged primitive, elongated skeletal muscle cells. The cells are set within a well-developed fibromyxoid stroma. A different pattern (intermediate type) is predominantly composed of cells with better differentiation towards skeletal muscle. There are often large ganglion cell-like rhabdomyoblasts showing prominent nucleoli within nuclei that show vesicular chromatin distribution. Another population includes strap-like rhabdomyoblasts with darkly staining pink cytoplasm. Nearly all tumors show short to more sweeping fascicles of spindled rhabdomyoblasts. The tumor cells may infiltrate into adjacent skeletal muscle or fat. It is not uncommon to see peri-neural association, although not perineural infiltration.[9] ## Diagnosis[edit] These tumors may be detected prenatally by ultrasound and MRI.[10] Additionally, preoperative fine needle aspiration can be used to diagnose the tumor.[11] ### Ancillary testing[edit] A phosphotungstic acid hematoxylin stain may be used to highlight cross striations in the cytoplasm of the tumor cells. PAS with diastase will highlight the presence of glycogen in the tumor cells' cytoplasm. Immunohistochemistry will yield a positive reaction with a variety of myoid markers, including desmin, myoglobin, myogenin, MYOD1 and muscle specific actin. They may also be positive with vimentin, smooth muscle actin, and Leu-7. However, the tumor cells are almost always negative with glial fibrillary acidic protein, S100 protein, cytokeratin, epithelial membrane antigen, CD68, FLI1, CD99 and CD56. Although not used as frequently now, electron microscopy will show thick and thin myofilaments, Z-bands: these are features of sarcometric differentiation.[12] ### Differential diagnosis[edit] The differential diagnosis histologically includes rhabdomyosarcoma, granular cell tumor, alveolar soft part sarcoma, hibernoma, oncocytoma, and crystal storing histiocytosis, among others.[13] ## Management[edit] Surgical excision is the treatment of choice.[14] Recurrences are reported, but this is usually due to incomplete removal initially.[15][16] There is no role for chemotherapy or radiation therapy. ## Epidemiology[edit] They present over a wide age range (birth to about 65 years), but within the head and neck region, about 50% of cases develop in patients younger than 15 years of age. Within the head and neck, males are affected about 2–3 times more often than females.[17] ## References[edit] 1. ^ Lapner PC, Chou S, Jimenez C. Perianal fetal rhabdomyoma: case report. Pediatr Surg Int 1997;12(7):544-7. 2. ^ Watson J, Depasquale K, Ghaderi M, Zwillenberg S. Nevoid basal cell carcinoma syndrome and fetal rhabdomyoma: a case study. Ear Nose Throat J 2004;83(10):716-8. 3. ^ Hardisson D, Jimenez-Heffernan JA, Nistal M, Picazo ML, Tovar JA, Contreras F. Neural variant of fetal rhabdomyoma and naevoid basal cell carcinoma syndrome. Histopathology 1996;29(3):247-52. 4. ^ Walsh SN, Hurt MA. Cutaneous fetal rhabdomyoma: a case report and historical review of the literature. Am J Surg Pathol 2008:Mar;32(3):485-91. 5. ^ Kapadia SB, Meis JM, Frisman DM, Ellis GL, Heffner DK. Fetal rhabdomyoma of the head and neck: a clinicopathologic and immunophenotypic study of 24 cases. Hum Pathol 1993;24(7):754-65. 6. ^ Willis J, Abdul-Karim FW, di Sant'Agnese PA. Extracardiac rhabdomyomas. Semin Diagn Pathol 1994;11(1):15-25. 7. ^ Willis J, Abdul-Karim FW, di Sant'Agnese PA. Extracardiac rhabdomyomas. Semin Diagn Pathol 1994;11(1):15-25. 8. ^ Kapadia SB, Meis JM, Frisman DM, Ellis GL, Heffner DK. Fetal rhabdomyoma of the head and neck: a clinicopathologic and immunophenotypic study of 24 cases. Hum Pathol 1993;24(7):754-65. 9. ^ Kapadia SB, Meis JM, Frisman DM, Ellis GL, Heffner DK. Fetal rhabdomyoma of the head and neck: a clinicopathologic and immunophenotypic study of 24 cases. Hum Pathol 1993;24(7):754-65. 10. ^ O'Callaghan MG, House M, Ebay S, Bhadelia R. Rhabdomyoma of the head and neck demonstrated by prenatal magnetic resonance imaging. J Comput Assist Tomogr 2005;29(1):130-2 11. ^ al Rikabi AC, al Kharfy T, al Sohaibani MO, al Samarrai AI. Fetal rhabdomyoma. A case report with the diagnosis suggested by intraoperative cytology. Acta Cytol 1996;40(4):786-8. 12. ^ Kapadia SB, Meis JM, Frisman DM, Ellis GL, Heffner DK. Fetal rhabdomyoma of the head and neck: a clinicopathologic and immunophenotypic study of 24 cases. Hum Pathol 1993;24(7):754-65. 13. ^ Kapadia SB, Meis JM, Frisman DM, Ellis GL, Heffner DK. Fetal rhabdomyoma of the head and neck: a clinicopathologic and immunophenotypic study of 24 cases. Hum Pathol 1993;24(7):754-65. 14. ^ Kapadia SB, Meis JM, Frisman DM, Ellis GL, Heffner DK. Fetal rhabdomyoma of the head and neck: a clinicopathologic and immunophenotypic study of 24 cases. Hum Pathol 1993;24(7):754-65. 15. ^ Valdez TA, Desai U, Volk MS. Recurrent fetal rhabdomyoma of the head and neck. Int J Pediatr Otorhinolaryngol 2006:70(6);1115-8. 16. ^ Smith NM, Thornton CM. Fetal rhabdomyoma: two instances of recurrence. Pediatr Pathol Lab Med 1996;16(4):673-80. 17. ^ Kapadia SB, Meis JM, Frisman DM, Ellis GL, Heffner DK. Fetal rhabdomyoma of the head and neck: a clinicopathologic and immunophenotypic study of 24 cases. Hum Pathol 1993;24(7):754-65. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Fetal rhabdomyoma	c0334482	3,953	wikipedia	https://en.wikipedia.org/wiki/Fetal_rhabdomyoma	2021-01-18T19:10:15	{"umls": ["C0334482"], "wikidata": ["Q5445911"]}
For a discussion of genetic heterogeneity of bone mineral density (BMD), see BMND1 (601884). Mapping Styrkarsdottir et al. (2008) performed a quantitative trait analysis of data from 5,861 Icelandic subjects, testing for an association between 301,019 single-nucleotide polymorphisms (SNPs) and bone mineral density of the hip or lumbar spine. The authors then tested for an association between 74 SNPs (most of which were implicated in the discovery set) at 32 loci in replication sets of Icelandic, Danish, and Australian subjects (4165, 2269, and 1491 subjects, respectively). Styrkarsdottir et al. (2008) found a complex pattern of association in the 6q25 region. SNPs in this region showed an association with bone mineral density of both hip and spine, although none of the SNPs could fully account for the associations. At least 3 SNPs, e.g., rs4870044, rs1038304, and rs1999805, seemed to be required to account for the overall association. The SNP rs1999805, located within an intron of a splice variant of the ESR1 gene (133430), achieved a combined P value of 2.2 x 10(-8), with an estimated effect of the C allele for bone mineral density of spine of -0.09 (95% CI = -0.12 to -0.06). The SNPs rs4870044 and rs1038304 are located 44 to 75 kb upstream of the ESR1 gene, within the C6ORF97 gene. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	BONE MINERAL DENSITY QUANTITATIVE TRAIT LOCUS 11	c2677497	3,954	omim	https://www.omim.org/entry/612114	2019-09-22T16:02:18	{"omim": ["612114"]}
A form of axonal Charcot-Marie-Tooth disease, a peripheral motor and sensory neuropathy, characterized by congenital pstosis and early cataract associated to a mildly progressive peripheral neuropathy of variable onset from birth to the 6th decade, pes cavus, reduced to absent ankles tendon reflexes and sometimes neutropenia. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Autosomal dominant Charcot-Marie-Tooth disease type 2M	c1847902	3,955	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=228179	2021-01-23T17:26:34	{"mesh": ["C564703"], "omim": ["606482"], "umls": ["C1847902"], "icd-10": ["G60.0"], "synonyms": ["CMT2M"]}
UV-sensitive syndrome is a condition that is characterized by sensitivity to the ultraviolet (UV) rays in sunlight. Even a small amount of sun exposure can cause a sunburn in affected individuals. In addition, these individuals can have freckles, dryness, or changes in coloring (pigmentation) on sun-exposed areas of skin after repeated exposure. Some people with UV-sensitive syndrome have small clusters of enlarged blood vessels just under the skin (telangiectasia), usually on the cheeks and nose. Although UV exposure can cause skin cancers, people with UV-sensitive syndrome do not have an increased risk of developing these forms of cancer compared with the general population. ## Frequency UV-sensitive syndrome appears to be a rare condition; only a small number of affected individuals have been reported in the scientific literature. However, this condition may be underdiagnosed. ## Causes UV-sensitive syndrome can result from mutations in the ERCC6 gene (also known as the CSB gene), the ERCC8 gene (also known as the CSA gene), or the UVSSA gene. These genes provide instructions for making proteins that are involved in repairing damaged DNA. DNA can be damaged by UV rays from the sun and by toxic chemicals, radiation, and unstable molecules called free radicals. Cells are usually able to fix DNA damage before it causes problems. If left uncorrected, DNA damage accumulates, which causes cells to malfunction and can lead to cell death. Cells have several mechanisms to correct DNA damage. The CSB, CSA, and UVSSA proteins are involved in one mechanism that repairs damaged DNA within active genes (those genes undergoing gene transcription, the first step in protein production). When DNA in active genes is damaged, the enzyme that carries out gene transcription (RNA polymerase) gets stuck, and the process stalls. Researchers think that the CSB, CSA, and UVSSA proteins help remove RNA polymerase from the damaged site, so the DNA can be repaired. Mutations in the ERCC6, ERCC8, or UVSSA genes lead to the production of an abnormal protein or the loss of the protein. If any of these proteins is not functioning normally, skin cells cannot repair DNA damage caused by UV rays, and transcription of damaged genes is blocked. However, it is unclear exactly how abnormalities in these proteins cause the signs and symptoms of UV-sensitive syndrome. ### Learn more about the genes associated with UV-sensitive syndrome * ERCC6 * ERCC8 * UVSSA ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	UV-sensitive syndrome	c3551173	3,956	medlineplus	https://medlineplus.gov/genetics/condition/uv-sensitive-syndrome/	2021-01-27T08:24:45	{"gard": ["10947"], "omim": ["600630", "614621", "614640"], "synonyms": []}
Hyperlipoproteinemia type 1 is an inherited condition that disrupts the normal breakdown of fats in the body, causing a large amount of fat to build up in the blood. This condition is characterized by inflammation of the pancreas (pancreatitis), abdominal pain, enlargement of the liver and spleen (hepatosplenomegaly), and small yellow skin lesions called eruptive xanthomas. Hyperlipoproteinemia type 1 is caused by mutations in the LPL gene. This condition is inherited in an autosomal recessive pattern. Treatment aims to control the symptoms through a low-fat diet. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Familial chylomicronemia syndrome	c0023817	3,957	gard	https://rarediseases.info.nih.gov/diseases/6414/familial-chylomicronemia-syndrome	2021-01-18T18:00:35	{"mesh": ["D008072"], "omim": ["238600"], "orphanet": ["444490"], "synonyms": ["Hyperlipoproteinemia type 1"]}
For a general phenotypic description and a discussion of genetic heterogeneity of chondrodysplasia punctata, see CDPX2 (302960). Clinical Features Rittler et al. (1990) described 7 sporadic cases of what appeared to be a new form of chondrodysplasia punctata. Two of the cases had previously been reported by Burck et al. (1980) and Burck (1982). The principal clinical manifestations in all of the patients were flat midface and nose, short limbs, and otherwise normal development. Consistent radiologic manifestations in the newborn were discrete calcific stippling, coronal clefts of vertebral bodies, short tibias, and short second and third metacarpal bones. Radiologic findings in the older child included shortness of the tibias and of the third and fourth metacarpals. The same disorder was reported by Haynes and Wangner (1951) and by Asanti and Heikel (1963). Savarirayan et al. (2004) reported long-term clinical and radiologic progression in 3 unrelated patients with the tibia-metacarpal form of chondrodysplasia punctata who had been followed for 37, 25, and 32 years, respectively. At follow-up, intellectual function was normal, physical function was well preserved, and there was marked resolution of several significant early radiographic features. Two patients had chronic serous otitis media during childhood which required tympanostomy tubes. One patient underwent lumbar laminectomy at age 26 for back pain related to spinal stenosis. One patient had hip dysplasia requiring orthopedic surgical intervention. All 3 had recurrent patella dislocation. Savarirayan et al. (2004) suggested that the long-term clinical and functional prognosis in this condition appears to be better than that expected based on initial clinical and radiologic findings. Shukla and Phadke (2015) described a 1.5-year-old Indian boy, born of unrelated parents, with features suggesting a severe form of the MT type of chondrodysplasia punctata. The patient had a length of 63 cm (-7 SD), with a head circumference of 43 cm (50th centile). He had midface retrusion, depressed nasal bridge, short and proximally placed second digits, trident hand, and mild pectus carinatum. Radiographic features included severe shortening of the first, fourth, and fifth metacarpals, all the distal phalanges, and the proximal phalanx of the second digit of the hands, as well as severe shortening of the first, second, and third metatarsals and all the phalanges of both feet. Additional radiographic features included rounded vertebral bodies with decreased height, axe-shaped iliac bones, short humerus, distal ulnar hypoplasia, short and bent femur with widened metaphyses, and longer fibula that overshot the tibia at the upper end. There was stippling of the carpals, metacarpals, and phalanges, and punctate calcification in the sacral area. ### Association with Maternal Systemic Lupus Erythematosus Elcioglu and Hall (1998) reported 2 sibs with features consistent with a diagnosis of either the metacarpal or the brachytelephalangic type (see 302950) of chondrodysplasia punctata, one of whom was stillborn at 36 weeks and the other at 24 weeks, from a mother with systemic lupus erythematosus (SLE; 152700). Austin-Ward et al. (1998) reported a child with chondrodysplasia punctata and other congenital anomalies resembling those associated with the use of oral anticoagulants, but with no history of exposure, again born to a mother with SLE. Elcioglu and Hall (1998) and Austin-Ward et al. (1998), as well as Toriello (1998) in a commentary on these 2 papers, concluded that there was an association between chondrodysplasia punctata and maternal SLE. Kozlowski et al. (2004) described 2 brothers with chondrodysplasia punctata, whose mother had longstanding lupus erythematosus and epilepsy, for which she had been treated with chloroquine and other therapeutic agents during both pregnancies. Kozlowski et al. (2004) pointed to 7 previously reported instances of the association between chondrodysplasia punctata and maternal SLE. Inheritance Of the 7 cases reported by Rittler et al. (1990), occurrence in both males and females, advanced paternal age in 1 case, and absence of parental consanguinity were compatible with autosomal dominant mutation. INHERITANCE \- Autosomal dominant HEAD & NECK Face \- Flat midface Nose \- Flat nose SKELETAL \- Discrete calcific stippling Spine \- Coronal clefts of vertebral bodies Limbs \- Patella dislocation \- Short tibiae Hands \- Short second and third or third and fourth metacarpals ▲ 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	CHONDRODYSPLASIA PUNCTATA, TIBIA-METACARPAL TYPE	c0432224	3,958	omim	https://www.omim.org/entry/118651	2019-09-22T16:43:21	{"doid": ["0060293"], "mesh": ["C562961"], "omim": ["118651"], "orphanet": ["79346"], "synonyms": ["Alternative titles", "CHONDRODYSPLASIA PUNCTATA, MT TYPE"]}
Richards-Rundle syndrome is an extremely rare neurodegenerative disorder characterized by progressive spinocerebellar ataxia, sensorineural hearing loss, and hypergonadotropic hypogonadism associated with additional neurological manifestations (such as peripheral muscle wasting, nystagmus, intellectual disability or dementia) and ketoaciduria. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Richards-Rundle syndrome	c0796136	3,959	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1399	2021-01-23T18:29:34	{"gard": ["8423"], "mesh": ["C535674"], "omim": ["245100"], "umls": ["C0796136"], "icd-10": ["G60.2"], "synonyms": ["Ketoaciduria-intellectual disability-ataxia-deafness syndrome", "Ketoaciduria-intellectual disability-ataxia-hearing loss syndrome"]}
This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Focal nodular hyperplasia" – news · newspapers · books · scholar · JSTOR (August 2007) (Learn how and when to remove this template message) Focal nodular hyperplasia Micrograph of focal nodular hyperplasia. H&E stain. SpecialtyGastroenterology Focal nodular hyperplasia (FNH) is a benign tumor of the liver (hepatic tumor), which is the second most prevalent tumor of the liver (the first is hepatic hemangioma). It is usually asymptomatic, rarely grows or bleeds, and has no malignant potential. This tumour was once often resected because it was difficult to distinguish from hepatic adenoma, but with modern multiphase imaging is usually now diagnosed by strict imaging criteria and not resected. ## Contents * 1 Presentation * 2 Pathophysiology * 3 Diagnosis * 4 Notes * 5 References * 6 External links ## Presentation[edit] Ultrasound of malformed vessels within the fibrous scar of FNH. Liver tumor types by relative incidence in adults in the United States, with focal nodular hyperplasia at right.[1] Focal nodular hyperplasia's most recognizable gross feature is a central stellate scar seen in 60–70% of cases. Microscopically, a lobular proliferation of bland-appearing hepatocytes with a bile ductular proliferation and malformed vessels within the fibrous scar is the most common pattern. Other patterns include telangiectatic, hyperplastic-adenomatous, and lesions with focal large-cell dysplasia.[2] Rarely, these lesions may be multiple or can occur as part of a syndrome with hemangiomas, epithelioid hemangioendothelioma, hepatic adenomas, fibrolamellar hepatocellular carcinoma, vascular malformations of the brain, meningiomas, and/or astrocytomas.[2] ## Pathophysiology[edit] FNH is not a true neoplasm; it is believed to result from localized hyperplastic hepatocyte response to an underlying congenital arteriovenous malformation. It consists of normal liver constituents in an abnormally organized pattern, grows in a stellate pattern and may display central necrosis when large.[3] Additionally evidence suggests that the incidence of FNH is related to oral contraceptive use.[4] ## Diagnosis[edit] Unenhanced CT or MRI usually does not show the difference in intensity between the FNH and surrounding liver except when there is marked liver steatosis that reduces the attenuation of the liver, causing FNH to be hyperattenuating when compared with the surrounding liver. In the arterial phase CT or MRI, there is a strong enhancement not followed by washout. The lesion presents a slight hyperintensity or isodensity on portal venous phase or delayed phase images. There is also a presence of a central scar and absence of a capsule for the FNH.[5] ## Notes[edit] 1. ^ Table 37.2 in: Sternberg, Stephen (2012). Sternberg's diagnostic surgical pathology. Place of publication not identified: LWW. ISBN 978-1-4511-5289-0. OCLC 953861627.CS1 maint: ref=harv (link) 2. ^ a b Nguyen, Bich N.; Fléjou, Jean-François; Terris, Benoit; Belghiti, Jacques; Degott, Claude (1999). "Focal Nodular Hyperplasia of the Liver". The American Journal of Surgical Pathology. 23 (12): 1441–54. doi:10.1097/00000478-199912000-00001. PMID 10584697. 3. ^ Imaging in Focal Nodular Hyperplasia at eMedicine 4. ^ Scalori, Astrid; Tavani, Alessandra; Gallus, Silvano; La Vecchia, Carlo; Colombo, Massimo (2002). "Oral contraceptives and the risk of focal nodular hyperplasia of the liver: A case-control study". American Journal of Obstetrics and Gynecology. 186 (2): 195–7. doi:10.1067/mob.2002.120277. PMID 11854634. 5. ^ Dioguardi Burgio, Marco; Ronot, Maxime; Salvaggio, Giuseppe; Vilgrain, Valérie; Brancatelli, Giuseppe (December 2016). "Imaging of Hepatic Focal Nodular Hyperplasia: Pictorial Review and Diagnostic Strategy". Seminars in Ultrasound, CT and MRI. 37 (6): 511–524. doi:10.1053/j.sult.2016.08.001. ## References[edit] * Chun Hsee, Li; McCall, John L.; Koea, Jonathan B. (2005). "Focal nodular hyperplasia: what are the indications for resection?". HPB. 7 (4): 298–302. doi:10.1080/13651820500273624. PMC 2043107. PMID 18333211. ## External links[edit] Classification D * ICD-10: K76.8 * MeSH: D020518 * DiseasesDB: 33467 External resources * eMedicine: radio/286 * v * t * e Digestive system neoplasia GI tract Upper Esophagus * Squamous cell carcinoma * Adenocarcinoma Stomach * Gastric carcinoma * Signet ring cell carcinoma * Gastric lymphoma * MALT lymphoma * Linitis plastica Lower Small intestine * Duodenal cancer * Adenocarcinoma Appendix * Carcinoid * Pseudomyxoma peritonei Colon/rectum * Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers Cronkhite–Canada * Polyposis syndromes: Juvenile * MUTYH-associated * Familial adenomatous/Gardner's * Polymerase proofreading-associated * Serrated polyposis * Neoplasm: Adenocarcinoma * Familial adenomatous polyposis * Hereditary nonpolyposis colorectal cancer Anus * Squamous cell carcinoma Upper and/or lower * Gastrointestinal stromal tumor * Krukenberg tumor (metastatic) Accessory Liver * malignant: Hepatocellular carcinoma * Fibrolamellar * Hepatoblastoma * benign: Hepatocellular adenoma * Cavernous hemangioma * hyperplasia: Focal nodular hyperplasia * Nodular regenerative hyperplasia Biliary tract * bile duct: Cholangiocarcinoma * Klatskin tumor * gallbladder: Gallbladder cancer Pancreas * exocrine pancreas: Adenocarcinoma * Pancreatic ductal carcinoma * cystic neoplasms: Serous microcystic adenoma * Intraductal papillary mucinous neoplasm * Mucinous cystic neoplasm * Solid pseudopapillary neoplasm * Pancreatoblastoma Peritoneum * Primary peritoneal carcinoma * Peritoneal mesothelioma * Desmoplastic small round cell tumor [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Focal nodular hyperplasia	c0333980	3,960	wikipedia	https://en.wikipedia.org/wiki/Focal_nodular_hyperplasia	2021-01-18T18:59:38	{"mesh": ["D020518"], "wikidata": ["Q1435219"]}
Optic neuropathy SpecialtyOphthalmology Optic neuropathy is damage to the optic nerve from any cause. Damage and death of these nerve cells, or neurons, leads to characteristic features of optic neuropathy. The main symptom is loss of vision, with colors appearing subtly washed out in the affected eye. On medical examination, the optic nerve head can be visualised by an ophthalmoscope. A pale disc is characteristic of long-standing optic neuropathy. In many cases, only one eye is affected and patients may not be aware of the loss of color vision until the doctor asks them to cover the healthy eye. Optic neuropathy is often called optic atrophy, to describe the loss of some or most of the fibers of the optic nerve. In medicine, "atrophy" usually means "shrunken but capable of regrowth", so some argue that "optic atrophy" as a pathological term is somewhat misleading and the term "optic neuropathy" should be used instead. In short, optic atrophy is the end result of any disease that damages nerve cells anywhere between the retinal ganglion cells and the lateral geniculate body (anterior visual system). ## Contents * 1 Causes * 1.1 Ischemic optic neuropathy * 1.2 Optic neuritis * 1.3 Compressive optic neuropathy * 1.4 Infiltrative optic neuropathy * 1.5 Traumatic optic neuropathy * 1.6 Mitochondrial optic neuropathies * 1.6.1 Nutritional optic neuropathies * 1.6.2 Toxic optic neuropathies * 1.6.3 Hereditary optic neuropathies * 2 Optic nerve * 3 Diagnosis * 4 See also * 5 References * 6 External links ## Causes[edit] ### Ischemic optic neuropathy[edit] In ischemic optic neuropathies, there is insufficient blood flow (ischemia) to the optic nerve. The anterior optic nerve is supplied by the short posterior ciliary artery and choroidal circulation, while the retrobulbar optic nerve is supplied intraorbitally by a pial plexus, which arises from the ophthalmic artery, internal carotid artery, anterior cerebral artery, and anterior communicating arteries. Ischemic optic neuropathies are classified based on the location of the damage and the cause of reduced blood flow, if known.[1] * Anterior ischemic optic neuropathy (AION) includes diseases that affect the optic nerve head and cause swelling of the optic disc. These diseases often cause sudden rapid visual loss in one eye. Inflammatory diseases of the blood vessels, like giant-cell arteritis, polyarteritis nodosa, Churg-Strauss syndrome, granulomatosis with polyangiitis, and rheumatoid arthritis can cause arteritic AIONs (AAION). The vast majority of AIONs are nonarteritic AIONs (NAION). The most common acute optic neuropathy in patients over 50 years of age, NAION has an annual incidence of 2.3-10.2/100,000. NAION presents as a painless loss of vision, often when awakening, that occurs over hours to days. Most patients lose the lower half of their visual field (an inferior altitudinal loss), though superior altitudinal loss is also common. The pathophysiology of NAION is unknown, but it is related to poor circulation in the optic nerve head. NAION is often associated with diabetes mellitus, elevated intraocular pressure (acute glaucoma, eye surgery), high cholesterol, hypercoagulable states, a drop in blood pressure (bleeding, cardiac arrest, peri-operative esp. cardiac and spine procedures), and sleep apnea. Rarely, amiodarone, interferon-alpha, and erectile dysfunction drugs have been associated with this disease. * Posterior ischemic optic neuropathy is a syndrome of sudden visual loss with optic neuropathy without initial disc swelling with subsequent development of optic atrophy. This can occur in patients who are predisposed to AAION and NAION as described above as well as those who had cardiac and spine surgery or serious episodes of hypotension. * Radiation optic neuropathy (RON) is also thought to be due to ischemia of the optic nerve that occurs 3 months to 8 or more years after radiation therapy to the brain and orbit. It occurs most often around 1.5 years after treatment and results in irreversible and severe vision loss, which may also be associated with damage to the retina (radiation retinopathy). This is thought to be due to damage to dividing glial and vascular endothelial cells. RON can present with transient visual loss followed by acute painless visual loss in one or both eyes several weeks later. The risk of RON is significantly increased with radiation doses over 50 Gy. * There is also some evidence that interferon treatment (pegylated interferon with ribavirin) for hepatitis C virus can cause optic neuropathy.[2] ### Optic neuritis[edit] Optic neuritis is inflammation of the optic nerve, which is associated with swelling and destruction of the myelin sheath covering the optic nerve. Young adults, usually females, are most commonly affected. Symptoms of optic neuritis in the affected eye include pain on eye movement, sudden loss of vision, and decrease in color vision (especially reds). Optic neuritis, when combined with the presence of multiple demyelinating white matter brain lesions on MRI, is suspicious for multiple sclerosis. Several causes and clinical courses are possible for the optic neuritis. It can be classified in: * Single isolated optic neuritis (SION) * relapsing isolated optic neuritis (RION) * chronic relapsing inflammatory optic neuropathy (CRION) * the neuromyelitis optica (NMO) spectrum disorder * multiple sclerosis associated optic neuritis (MSON) * unclassified optic neuritis (UCON) forms.[3] Medical examination of the optic nerve with an ophthalmoscope may reveal a swollen optic nerve, but the nerve may also appear normal. Presence of an afferent pupillary defect, decreased color vision, and visual field loss (often central) are suggestive of optic neuritis. Recovery of visual function is expected within 10 weeks. However, attacks may lead to permanent axonal loss and thinning of the retinal nerve fiber layer. ### Compressive optic neuropathy[edit] Tumors, infections, and inflammatory processes can cause lesions within the orbit and, less commonly, the optic canal. These lesions may compress the optic nerve, resulting optic disc swelling and progressive visual loss. Implicated orbital disorders include optic gliomas, meningiomas, hemangiomas, lymphangiomas, dermoid cysts, carcinoma, lymphoma, multiple myeloma, inflammatory orbital pseudotumor, and thyroid ophthalmopathy. Patients often have bulging out of the eye (proptosis) with mild color deficits and almost normal vision with disc swelling. ### Infiltrative optic neuropathy[edit] The optic nerve can be infiltrated by a variety of processes, including tumors, inflammation, and infections. Tumors that can infiltrate the optic nerve can be primary (optic gliomas, capillary hemangiomas, and cavernous hemangiomas) or secondary (metastatic carcinoma, nasopharyngeal carcinoma, lymphoma, and leukemia). The most common inflammatory disorder that infiltrates the optic nerve is sarcoidosis. Opportunistic fungi, viruses, and bacteria may also infiltrate the optic nerve. The optic nerve may be elevated if the infiltration occurs in the proximal portion of the nerve. The appearance of the nerve on examination depends on the portion of the nerve that is affected. ### Traumatic optic neuropathy[edit] The optic nerve can be damaged when exposed to direct or indirect injury. Direct optic nerve injuries are caused by trauma to the head or orbit that crosses normal tissue planes and disrupts the anatomy and function of the optic nerve; e.g., a bullet or forceps that physically injures the optic nerve. Indirect injuries, like blunt trauma to the forehead during a motor vehicle accident, transmit force to the optic nerve without transgressing tissue planes. This type of force causes the optic nerve to absorb excess energy at the time of impact. The most common site of injury of the optic nerve is the intracanalicular portion of the nerve. Deceleration injuries from motor vehicle or bicycle accidents account for 17 to 63 percent of cases. Falls are also a common cause, and optic neuropathy most commonly occurs when there is a loss of consciousness associated with multi-system trauma and serious brain injury. In less than three percent of patients, an orbital hemorrhage after an injection behind the eye (retrobulbar block) can cause injury to the optic nerve, but this is readily manageable if it does not involve direct optic nerve injury and is caught early. The role of high-dose steroids and orbital decompression in treating these patients is controversial and, if administered, must be done very soon after injury with minimal effects. In patients with an orbital fracture, vomiting or nose blowing can force air into the orbit and possibly compromise the integrity of the optic nerve. ### Mitochondrial optic neuropathies[edit] Mitochondria play a central role in maintaining the life cycle of retinal ganglion cells because of their high energy dependence. Mitochondria are made within the central somata of the retinal ganglion cell, transported down axons, and distributed where they are needed. Genetic mutations in mitochondrial DNA, vitamin depletion, alcohol and tobacco abuse, and use of certain drugs can cause derangements in efficient transport of mitochondria, which can cause a primary or secondary optic neuropathy.[4] #### Nutritional optic neuropathies[edit] A nutritional optic neuropathy may be present in a patient with obvious evidence of under-nutrition (weight loss and wasting). Months of depletion are usually necessary to deplete body stores of most nutrients. Undernourished patients often suffer from many vitamin and nutrient deficiencies and have low serum protein levels. However, the optic neuropathy associated with pernicious anemia and vitamin B12 deficiency can even be seen in well-nourished individuals. Gastric bypass surgery may also cause a vitamin B12 deficiency from poor absorption. Patients who suffer from nutritional optic neuropathy may notice that colors are not as vivid or bright as before and that the color red is washed out. This normally occurs in both eyes at the same time and is not associated with any eye pain. They might initially notice a blur or fog, followed by a drop in vision. While vision loss may be rapid, progression to blindness is unusual. These patients tend to have blind spots in the center of their vision with preserved peripheral vision. In most cases, the pupils continue to respond normally to light. Nutritional deficiencies affect the whole body, so pain or loss of sensation in the arms and legs (peripheral neuropathy) is often seen in patients with nutritional optic neuropathies. There was an epidemic of nutritional optic neuropathy among afflicted Allied prisoners of war of the Japanese during World War II. After four months of food deprivation, the prisoners of war developed vision loss in both eyes that appeared suddenly. They also had pain in their extremities and hearing loss. There is an endemic tropical neuropathy in Nigeria that may be due to a nutritional deficiency, but this has not been proven. #### Toxic optic neuropathies[edit] The most recognized cause of a toxic optic neuropathy is methanol poisoning. This can be a life-threatening event that normally accidentally occurs when the victim mistook, or substituted, methanol for ethyl alcohol. Blindness can occur with drinking as little as an ounce of methanol, but this can be counteracted by concurrent drinking of ethyl alcohol. The patient initially has nausea and vomiting, followed by respiratory distress, headache, and visual loss 18–48 hours after consumption. Without treatment, patients can go blind, and their pupils will dilate and stop reacting to light. * Ethylene glycol, a component of automobile antifreeze, is a poison that is toxic to the whole body including the optic nerve. Consumption can be fatal, or recovery can occur with permanent neurologic and ophthalmologic deficits. While visual loss is not very common, increased intracranial pressure can cause bilateral optic disc swelling from cerebral edema. A clue to the cause of intoxication is the presence of oxalate crystals in the urine. Like methanol intoxication, treatment is ethanol consumption. * Ethambutol, a drug commonly used to treat tuberculosis, is notorious for causing toxic optic neuropathy. Patients with vision loss from ethambutol toxicity lose vision in both eyes equally. This initially presents with problems with colors (dyschromatopsia) and can leave central visual deficits. If vision loss occurs while using ethambutol, it would be best to discontinue this medication under a doctor’s supervision. Vision can improve slowly after discontinuing ethambutol but rarely returns to baseline. * Amiodarone is an antiarrhythmic medication commonly used for abnormal heart rhythms (atrial or ventricular tachyarrythmias). Most patients on this medication get corneal epithelial deposits, but this medication has also been controversially associated with NAION. Patients on amiodarone with new visual symptoms should be evaluated by an ophthalmologist. * Tobacco exposure, most commonly through pipe and cigar smoking, can cause an optic neuropathy. Middle-aged or elderly men are often affected and present with painless, slowly progressive, color distortion and visual loss in both eyes. The mechanism is unclear, but this has been reported to be more common in individuals who are already suffering from malnutrition. #### Hereditary optic neuropathies[edit] The inherited optic neuropathies typically manifest as symmetric bilateral central visual loss. Optic nerve damage in most inherited optic neuropathies is permanent and progressive. * Leber’s hereditary optic neuropathy (LHON) is the most frequently occurring mitochondrial disease, and this inherited form of acute or subacute vision loss predominantly affects young males. LHON usually presents with rapid vision loss in one eye followed by involvement of the second eye (usually within months). Visual acuity often remains stable and poor (around or below 20/200) with a residual central visual field defect. Patients with the 14484/ND6 mutation are most likely to have visual recovery.[5] * Dominant optic atrophy is an autosomal dominant disease caused by a defect in the nuclear gene OPA1. A slowly progressive optic neuropathy, dominant optic atrophy, usually presents in the first decade of life and is bilaterally symmetrical. Examination of these patients shows loss of visual acuity, temporal pallor of the optic discs, centrocecal scotomas with peripheral sparing, and subtle impairments in color vision. * Behr’s syndrome is a rare autosomal recessive disorder characterized by early-onset optic atrophy, ataxia, and spasticity. * Berk–Tabatznik syndrome is a condition that shows symptoms of short stature, congenital optic atrophy and brachytelephalangy. This condition is extremely rare.[6] ## Optic nerve[edit] Main article: Optic nerve The optic nerve contains axons of nerve cells that emerge from the retina, leave the eye at the optic disc, and go to the visual cortex where input from the eye is processed into vision. There are 1.2 million optic nerve fibers that derive from the retinal ganglion cells of the inner retina.[7] ## Diagnosis[edit] This section is empty. You can help by adding to it. (April 2018) ## See also[edit] * Optic neuritis * Ophthalmoplegia * Glaucoma * Toxic and nutritional optic neuropathy ## References[edit] 1. ^ Neil R. Miller, Nancy J. Newman, Valérie Biousse, John B. Kerrison. Walsh & Hoyt's Clinical Neuro-Ophthalmology: The Essentials. Lippincott Williams & Wilkins, 2007.[page needed] 2. ^ Berg, Kathleen T; Nelson, Bruce; Harrison, Andrew R; McLoon, Linda K; Lee, Michael S (2010). "Pegylated Interferon Alpha-Associated Optic Neuropathy". Journal of Neuro-Ophthalmology. 30 (2): 117–22. doi:10.1097/WNO.0b013e3181d8e4af. PMC 3752854. PMID 20351572. 3. ^ Petzold, Axel; Plant, Gordon T (2014). "Diagnosis and classification of autoimmune optic neuropathy". Autoimmunity Reviews. 13 (4–5): 539–45. doi:10.1016/j.autrev.2014.01.009. PMID 24424177. 4. ^ Carelli, Valerio; Ross-Cisneros, Fred N; Sadun, Alfredo A (2004). "Mitochondrial dysfunction as a cause of optic neuropathies". Progress in Retinal and Eye Research. 23 (1): 53–89. doi:10.1016/j.preteyeres.2003.10.003. PMID 14766317. 5. ^ Oostra, R. J; Bolhuis, P. A; Wijburg, F. A; Zorn-Ende, G; Bleeker-Wagemakers, E. M (1994). "Leber's hereditary optic neuropathy: Correlations between mitochondrial genotype and visual outcome". Journal of Medical Genetics. 31 (4): 280–6. doi:10.1136/jmg.31.4.280. PMC 1049799. PMID 8071952. 6. ^ Genetic and Rare Diseases Information Center (GARD). "Berk-Tabatznik syndrome". Retrieved 28 September 2013. 7. ^ Sadun, Alfredo A (2009). "Neuroanatomy of the human visual system: Part I Retinal projections to the LGN and pretectum as demonstrated with a new method". Neuro-Ophthalmology. 6 (6): 353–61. doi:10.3109/01658108609016475. ## External links[edit] Classification D * ICD-10: H46 * MeSH: D009901 External resources * MedlinePlus: 001622 * Patient UK: Optic neuropathy * NCBI Genetic Testing Registry * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Optic neuropathy	c0029132	3,961	wikipedia	https://en.wikipedia.org/wiki/Optic_neuropathy	2021-01-18T19:00:18	{"mesh": ["D009901"], "umls": ["C0029132"], "icd-10": ["H46"], "wikidata": ["Q2879095"]}
A number sign (#) is used with this entry because X-linked cone-rod dystrophy-1 (CORDX1) and cone dystrophy-1 (COD1) are caused by mutation in an alternative terminal exon 15 (ORF15) of the RPGR gene (312610), which maps to chromosome Xp11. Description X-linked cone-rod dystrophy is a rare, progressive visual disorder primarily affecting cone photoreceptors (Demirci et al., 2002). Affected individuals, essentially all of whom are males, present with decreased visual acuity, myopia, photophobia, abnormal color vision, full peripheral visual fields, decreased photopic electroretinographic responses, and granularity of the macular retinal pigment epithelium. The degree of rod photoreceptor involvement is variable, with increasing degeneration. Although penetrance appears to be nearly 100%, there is variable expressivity with respect to age at onset, severity of symptoms, and findings (Hong et al., 1994). ### Genetic Heterogeneity of X-linked Cone-Rod Dystrophy Additional forms of X-linked cone-rod dystrophy include CORDX2 (300085), mapped to chromosome Xq27, and CORDX3 (300476), caused by mutation in the CACNA1F gene (300110) on chromosome Xp11.23. For a discussion of autosomal forms of cone-rod dystrophy, see CORD2 (120970). Clinical Features Cone dysfunction may be suspected if there is photophobia, fine nystagmus, reduced visual acuity, and abnormal color vision. (Patients with predominantly rod disease complain of difficulty with night vision and in the early stage of the disease may have normal visual acuity and color vision.) Although in some cases the diagnosis can be made on the basis of history and clinical examination, further tests of rod and cone function by special electrodiagnostic methods are often needed. These are important not only for diagnosis but also for recognition of the carrier state in X-linked dystrophies. Pinckers et al. (1981) and Pinckers and Timmerman (1981) reported 2 families with X-linked cone dystrophy. According to Pinckers (1982), the disorder begins as a peripheral cone disease and progresses to a diffuse cone disease. Affected males present with diminished visual acuity, myopia, disturbed cone ERG, and a type I color vision defect. Heterozygous females have diminished visual acuity and myopia, but a normal cone ERG and normal color vision. In a Dutch family with X-linked cone dystrophy in 5 generations, routine ophthalmologic examination showed no abnormalities in carriers, but detailed color vision testing detected 87% of obligate heterozygotes. Onset of visual deterioration in affected males occurred after age 20, with only one exception. It was preceded by marked pseudoprotanomaly in the patients who still had normal visual acuity. Pseudoprotanomaly was the label attached also to the functional derangement detected in carrier females (van Everdingen et al., 1992). Fleischman and O'Donnell (1981) reported another family as incomplete achromatopsia. Pinckers and Deutman (1987) suggested that this was the same disorder as that reported by Pinckers et al. (1981). The X-linked recessive cone dystrophy reported by Heckenlively and Weleber (1986) differed in its symptomatology and may be a distinct entity; see 304030. Pinckers and Deutman (1987) suggested that X-linked cone dystrophy may be much more frequent than generally realized. Among 25 patients with diffuse cone disease, 22 were males. Fleischman and O'Donnell (1981) studied a black kindred with 9 affected males and 7 carrier females. They concluded that this disorder is a slowly progressive abiotrophy, with progressive macular scarring and cone dysfunction, rather than a stationary anomaly. Some carrier females have ophthalmoscopic and fluorescein angiographic abnormalities in the macula. The extent of rod and cone involvement among affected males was quite variable in the family described by Hong et al. (1994). Although all the affected demonstrated some of the symptoms and features generally associated with primary cone abnormalities, such as photophobia, color-vision deficits, and central scotomas, significant rod dysfunction was also observed. The scotopic electroretinography of the proband was more impaired than the photopic responses, while the other affected males continued to show some rod function even when cone responses were nearly extinguished. All but 1 of the affected males examined had moderate to high myopia. Most of the affected males lost central vision in their late teens or early twenties, although 1 reported normal vision until the age of 35 years. Funduscopic examination ranged from normal to severe macular atrophy to widespread retinal degeneration (as illustrated in their Figure 2). One example of a 'bull's eye' macula was illustrated. The most common symptom among carrier women was photophobia under normal daylight conditions. Many noted difficulties with light adaptation and/or night vision. Holopigian et al. (2002) compared the patterns of local cone and rod system impairment in patients with progressive cone dystrophy using psychophysical and electrophysiologic techniques. The authors found poor correspondence among local measures of cone and rod system losses in their patients with progressive cone dystrophy. The results suggested that the spatial pattern of cone system losses in progressive cone dystrophy differed from the spatial pattern of rod system losses. Because of the disturbance of color vision, the cone dystrophies are sometimes labeled as incomplete achromatopsia; such is a symptom, not a primary diagnosis. The term incomplete achromatopsia is also used at times for blue cone monochromatism (303700). Jalkanen et al. (2003) tabulated the genetic and clinical features of X-linked recessive cone-rod dystrophies. Clinical Management Park and Sunness (2004) reported that red contact lenses successfully alleviated photophobia in patients with cone disorders. Mapping Linkage studies by Fleischman and O'Donnell (1981) showed negative lod scores with Xg blood group, but positive lod scores (maximum = 0.84) at a recombination fraction of 0.05 with G6PD. Bartley et al. (1989) found close linkage to DXS84, which is located between DXS7 and DXS206; maximum lod = 3.01 at theta = 0.00. These findings place the CORDX1 gene in the region Xp21.1-p11.3. Bergen et al. (1993) found close linkage without recombination between CORDX1 and the loci DXS84, MAOB, DXS164, DMD, and DXS436, with a maximum lod score of 2.1, confirming that the CORDX1 gene is in the Xp21.1-p11.3 region. Bergen et al. (1994) reported the first instance of carrier detection by DNA-based linkage. They warned that since X-linked cone dystrophy may be genetically heterogeneous, carrier detection by DNA analysis may only be carried out in those families in which the position of the gene locus can be clearly established. Indeed, Bergen and Pinckers (1997) found that the family with progressive cone dystrophy reported by Pinckers and Timmerman (1981) showed linkage not to Xp but to Xq27 (CORDX2; 300085). Hong et al. (1994) performed linkage analysis in a 4-generation family with X-linked progressive cone degeneration and found no recombination between the disease and the marker loci DXS7 and MAOA (309850), suggesting that the location of CORDX1 is in the Xp11.3 region, distal to DXS84 and proximal to ARAF1 (311010). Demirci et al. (2002) reevaluated 3 families with CORDX1 from the study of Seymour et al. (1998), which had mapped CORDX1 to Xp11.4, using new markers and clinically reassessing all key recombinants. They determined that critical intervals in 2 of the families overlapped the locus for retinitis pigmentosa-3 (RP3; 300029), which is caused by mutation in the RPGR gene (312610). In the third family the status change from affected to probably unaffected of a key recombinant individual reassigned the disease locus to include RP3 as well. Molecular Genetics Demirci et al. (2002) performed mutation analysis of the entire RPGR coding region in the families studied by Seymour et al. (1998) and identified 2 different 2-nucleotide deletions in open reading frame 15 (ORF15), in family 2 (delAG; 312610.0015) and in families 1 and 3 (delGG; 312610.0014), both of which resulted in a frameshift leading to altered amino acid structure and early termination. In addition, an unrelated individual with X-linked cone-rod dystrophy demonstrated a 1-nucleotide insertion (insA) in ORF15. The presence of 3 distinct mutations associated with the same disease phenotype provided strong evidence that mutations in RPGR exon ORF15 are responsible for CORDX1. Genetic heterogeneity exists, however, because of findings in 3 other families. Yang et al. (2002) mapped 2 Caucasian families of northern European ancestry with X-linked cone dystrophy to the CORDX1 locus on Xp, and identified mutations in ORF15 of the RPGR gene in each: ORF15+1343-1344delGG (312610.0014) and ORF15+694-708del15 (312610.0017). The latter mutation was predicted to delete 5 amino acids from the C-terminal region of the protein. Ebenezer et al. (2005) identified novel RPGR ORF15 protein truncation mutations in 2 of 6 families with CORDX1. In family A, a 2-bp mutation predicted to result in a truncated protein was identified (312610.0021). In family B, a G-to-T transversion resulted in a nonsense mutation (312610.0022). Phenotypic characteristics in both families included progressive deterioration of central vision and subsequently night vision, mild photophobia, and moderate to high myopia. Ophthalmoscopic abnormalities were generally confined to the macula: a parafoveal ring of increased autofluorescence was observed and electrophysiologic evidence of greater generalized abnormality in cone than rod responses were consistent with a cone-rod dystrophy phenotype. Eyes \- Cone dysfunction \- Photophobia \- Fine nystagmus \- Reduced visual acuity \- Type I color vision defect \- Myopia Misc \- Diminished visual acuity and myopia in heterozygous females Lab \- Disturbed cone ERG \- Progressive macular scarring Inheritance \- ? X-linked ▲ 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	CONE-ROD DYSTROPHY, X-LINKED, 1	c1844776	3,962	omim	https://www.omim.org/entry/304020	2019-09-22T16:18:29	{"doid": ["0111008"], "mesh": ["C564438"], "omim": ["304020", "120970"], "orphanet": ["1872"], "synonyms": []}
Main article: Tick-borne meningoencephalitis Powassan encephalitis SpecialtyInfectious disease Powassan encephalitis, caused by the Powassan virus (POWV), a flavivirus also known as the deer tick virus, is a form of arbovirus infection that results from tick bites. It can occur as a co-infection with Lyme disease since both are transmitted to humans by the same species of tick.[1] There has been a surge in the number of cases and geographic range in the last decade. In the United States, cases have been recorded in the northeast.[2] The disease was first isolated from the brain of a boy who died of encephalitis in Powassan, Ontario, in 1958.[3] The disease is a zoonosis, an animal disease, usually found in rodents and ticks, with spillover transmission to humans. The virus is antigenically related to the Far Eastern tick-borne encephalitis viruses.[4] ## Contents * 1 Presentation * 2 Diagnosis * 3 Treatment * 4 Prognosis * 5 References * 6 External links ## Presentation[edit] Symptoms manifest within 7–10 days and include fever, headache, partial paralysis, confusion, nausea and even coma. ## Diagnosis[edit] This section is empty. You can help by adding to it. (November 2017) ## Treatment[edit] There is currently no established treatment.[5] ## Prognosis[edit] Half of all cases results in permanent neurological damage and 10-15% result in death.[citation needed] ## References[edit] 1. ^ Caulfield, AJ; Pritt, BS (December 2015). "Lyme Disease Coinfections in the United States". Clinics in Laboratory Medicine. 35 (4): 827–46. doi:10.1016/j.cll.2015.07.006. PMID 26593260. 2. ^ "Cumulative human disease cases reported to CDC ArboNET for 2015". United States Geological Survey. Archived from the original on 2016-12-15. Retrieved 2015-11-27. 3. ^ McLEAN, DM; DONOHUE, WL (1 May 1959). "Powassan virus: isolation of virus from a fatal case of encephalitis". Canadian Medical Association Journal. 80 (9): 708–11. PMC 1830849. PMID 13652010. 4. ^ CASALS, J (13 February 1960). "Antigenic relationship between Powassan and Russian spring-summer encephalitis viruses". Canadian Medical Association Journal. 82: 355–8. PMC 1937779. PMID 13808112. 5. ^ Hinten SR, Beckett GA, Gensheimer KF, et al. (December 2008). "Increased recognition of Powassan encephalitis in the United States, 1999-2005". Vector Borne Zoonotic Dis. 8 (6): 733–40. doi:10.1089/vbz.2008.0022. PMID 18959500. ## External links[edit] Classification D * ICD-10: A84.8 * v * t * e Zoonotic viral diseases (A80–B34, 042–079) Arthropod -borne Mosquito -borne Bunyavirales * Arbovirus encephalitides: La Crosse encephalitis * LACV * Batai virus * BATV * Bwamba Fever * BWAV * California encephalitis * CEV * Jamestown Canyon encephalitis * Tete virus * Tahyna virus * TAHV * Viral hemorrhagic fevers: Rift Valley fever * RVFV * Bunyamwera fever * BUNV * Ngari virus * NRIV Flaviviridae * Arbovirus encephalitides: Japanese encephalitis * JEV * Australian encephalitis * MVEV * KUNV * Saint Louis encephalitis * SLEV * Usutu virus * West Nile fever * WNV * Viral hemorrhagic fevers: Dengue fever * DENV-1-4 * Yellow fever * YFV * Zika fever * Zika virus Togaviridae * Arbovirus encephalitides: Eastern equine encephalomyelitis * EEEV * Western equine encephalomyelitis * WEEV * Venezuelan equine encephalomyelitis * VEEV * Chikungunya * CHIKV * O'nyong'nyong fever * ONNV * Pogosta disease * Sindbis virus * Ross River fever * RRV * Semliki Forest virus Reoviridae * Banna virus encephalitis Tick -borne Bunyavirales * Viral hemorrhagic fevers: Bhanja virus * Crimean–Congo hemorrhagic fever (CCHFV) * Heartland virus * Severe fever with thrombocytopenia syndrome (Huaiyangshan banyangvirus) * Tete virus Flaviviridae * Arbovirus encephalitides: Tick-borne encephalitis * TBEV * Powassan encephalitis * POWV * Viral hemorrhagic fevers: Omsk hemorrhagic fever * OHFV * Kyasanur Forest disease * KFDV * AHFV * Langat virus * LGTV Orthomyxoviridae * Bourbon virus Reoviridae * Colorado tick fever * CTFV * Kemerovo tickborne viral fever Sandfly -borne Bunyavirales * Adria virus (ADRV) * Oropouche fever * Oropouche virus * Pappataci fever * Toscana virus * Sandfly fever Naples virus Rhabdoviridae * Chandipura virus Mammal -borne Rodent -borne Arenaviridae * Viral hemorrhagic fevers: Lassa fever * LASV * Venezuelan hemorrhagic fever * GTOV * Argentine hemorrhagic fever * JUNV * Brazilian hemorrhagic fever * SABV * Bolivian hemorrhagic fever * MACV * LUJV * CHPV Bunyavirales * Hemorrhagic fever with renal syndrome * DOBV * HTNV * PUUV * SEOV * AMRV * THAIV * Hantavirus pulmonary syndrome * ANDV * SNV Herpesviridae * Murid gammaherpesvirus 4 Bat -borne Filoviridae * BDBV * SUDV * TAFV * Marburg virus disease * MARV * RAVV Rhabdoviridae * Rabies * ABLV * MOKV * DUVV * LBV * CHPV Paramyxoviridae * Henipavirus encephalitis * HeV * NiV Coronaviridae * SARS-related coronavirus * SARS-CoV * MERS-CoV * SARS-CoV-2 Primate -borne Herpesviridae * Macacine alphaherpesvirus 1 Retroviridae * Simian foamy virus * HTLV-1 * HTLV-2 Poxviridae * Tanapox * Yaba monkey tumor virus Multiple vectors Rhabdoviridae * Rabies * RABV * Mokola virus Poxviridae * Monkeypox * 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 This article about a medical condition affecting the nervous system is a stub. You can help Wikipedia by expanding it. * v * t * e [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Powassan encephalitis	c0032858	3,963	wikipedia	https://en.wikipedia.org/wiki/Powassan_encephalitis	2021-01-18T19:05:46	{"mesh": ["D004675"], "icd-10": ["A84.8"], "wikidata": ["Q7235947"]}
Spastic paraplegia-severe developmental delay-epilepsy syndrome is a rare, genetic, complex spastic paraplegia disorder characterized by an infantile-onset of psychomotor developmental delay with severe intellectual disability and poor speech acquisition, associated with seizures (mostly myoclonic), muscular hypotonia which may be noted at birth, and slowly progressive spasticity in the lower limbs leading to severe gait disturbances. Ocular abnormalities and incontinence are commonly associated. Other symptoms may include verbal dyspraxia, hypogenitalism, macrocephaly and sensorineural hearing loss, as well as dystonic movements and ataxia with upper limb involvement. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Spastic paraplegia-severe developmental delay-epilepsy syndrome	c4225215	3,964	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=464282	2021-01-23T17:03:01	{"omim": ["616756"], "synonyms": ["SPPRS syndrome", "Spastic paraplegia-psychomotor retardation-seizures syndrome"]}
Cohan et al. (1979) described adult Ethiopian brother and sister with this combination. Eyes \- Retinal degeneration Neuro \- Seizures Inheritance \- Autosomal recessive ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: 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 DEGENERATION AND EPILEPSY	c1849416	3,965	omim	https://www.omim.org/entry/267740	2019-09-22T16:22:44	{"mesh": ["C564847"], "omim": ["267740"]}
Prion protein (PrP) systemic amyloidosis, previously known as chronic diarrhea with hereditary sensory and autonomic neuropathy is an extremely rare autosomal dominant disorder reported in three British families, a Japanese and an Italian family (about 16 cases in total). Onset is usually in the fourth decade of life and the course lasts about 20 years. Reported clinical manifestations include diarrhea, nausea, autonomic failure (areflexia, weakness), neurogenic bladder and urinary infections. The disorder is caused by truncation mutations of the prion protein gene PRNP (20p13) leading to deposition of prion protein amyloid. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	PrP systemic amyloidosis	c4518776	3,966	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=397606	2021-01-23T17:51:40	{"icd-10": ["G60.8"], "synonyms": ["Chronic diarrhea with HSAN", "Chronic diarrhea with hereditary sensory and autonomic neuropathy", "Prion protein systemic amyloidosis"]}
## Description Idiopathic scoliosis is a structurally fixed lateral curvature of the spine with a rotatory component. There is at least a 10 degree curvature as demonstrated by upright spine roentgenograms by the Cobb method (Weinstein, 1994). For a discussion of genetic heterogeneity of isolated scoliosis, see IS1 (181800). Clinical Features Ocaka et al. (2008) reported 2 unrelated British families with autosomal dominant adolescent scoliosis. The first family had 10 affected members, spanned 4 generations, and had disease severity ranging from 11 to 40 degrees curvature. The second family had 6 affected members, spanned 2 generations, and had disease severity ranging from 14 to 55 degrees curvature. Mapping By genomewide linkage analysis of 2 unrelated British families with autosomal dominant scoliosis, Ocaka et al. (2008) identified a region on chromosome 17q25.3 that segregated with disease in both families. A cumulative 2-point lod score of 4.08 was obtained for both families at marker AAT095. Subsequent fine mapping and refinement of the locus yielded an affected-only cumulative 2-point lod score of 3.79 at marker D17928 and a multipoint score of 3.78 between marker D17S914 and 17qter. Haplotype analysis identified a 9.6-cM candidate interval between D17S1806 and 17qter. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	SCOLIOSIS, ISOLATED, SUSCEPTIBILITY TO, 5	c2677107	3,967	omim	https://www.omim.org/entry/612239	2019-09-22T16:02:04	{"omim": ["612239"]}
A number sign (#) is used with this entry because mitochondrial DNA (mtDNA) depletion syndrome-2 (MTDPS2) is caused by homozygous or compound heterozygous mutation in the mitochondrial thymidine kinase gene (TK2; 188250) on chromosome 16q21. Description Mitochondrial DNA depletion syndrome-2 is an autosomal recessive disorder characterized primarily by childhood onset of muscle weakness associated with depletion of mtDNA in skeletal muscle. There is wide clinical variability; some patients have onset in infancy and show a rapidly progressive course with early death due to respiratory failure, whereas others have later childhood onset of a slowly progressive myopathy (Oskoui et al., 2006). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). Clinical Features Boustany et al. (1983) reported a female infant with a fatal mitochondrial myopathy characterized by progressive generalized hypotonia, progressive external ophthalmoplegia, and severe lactic acidosis. Electron microscopy of skeletal muscle in the proband showed marked proliferation of enlarged mitochondria, many containing concentric rings of cristae, and biochemical studies showed severely decreased cytochrome c oxidase activity (less than 1% of normal). Mitochondria from kidney, liver, heart, lung, and brain examined postmortem had normal cytochromes and preserved cytochrome c oxidase activity. A second cousin, related through the maternal grandfather, died at 9 months of hepatic failure with generalized aminoaciduria, but without lactic acidosis or muscle involvement, consistent with the hepatocerebral form of the disorder. In the second cousin, liver biopsy showed enlarged mitochondria and decreased cytochrome c oxidase activity (less than 10% of normal). Kidney mitochondria showed normal cytochromes. In an addendum, the authors noted that a sister of the proband presented at 2 months of age with hypotonia, ophthalmoplegia, and lactic acidosis. Findings of electron microscopy and biochemical analysis of muscle and liver biopsy specimens were identical to those in the proband. In tissue samples from the original proband and second cousin reported by Boustany et al. (1983), Moraes et al. (1991) found a quantitative defect of mtDNA restricted to skeletal muscle (2% of control values) in the proband, and involving liver (12% of control values) in the second cousin. A third unrelated patient had mtDNA deficiency in muscle only (3% of control values), and a fourth in muscle and kidney only (17% control values in both tissues). There was no evidence of an mtDNA mutation in the areas surrounding the origin of replication of the heavy strand (H-strand) or light strand (L-strand) of mtDNA. Moraes et al. (1991) concluded that affected individuals exhibit variable levels of mtDNA depletion (up to 98%) in affected tissues, while unaffected tissues have relatively normal levels of mtDNA. In addition, different tissues may be involved in related patients. Tritschler et al. (1992) reported 5 children with mitochondrial myopathy manifesting within or soon after the first year of life. Muscle biopsies showed ragged-red fibers and decreased respiratory chain activity associated with a decreased amount (2 to 34% of normal) of muscle mitochondrial DNA. Vila et al. (2003) described an unusual case of a 14-year-old boy with the myopathic form of the disorder who was a compound heterozygote for mutations in the TK2 gene. Symptoms were manifest since birth, and muscle examination at ages 3 and 8 years showed ragged-red fibers, deficiency of cytochrome c oxidase, and severe depletion of mtDNA. Activities of mitochondrial respiratory chain enzymes at that time were normal. Reexamination at age 14 years showed progression of the disease and muscle biopsy showed severe muscle atrophy, no mtDNA depletion, and decreased activities of all respiratory chain enzymes. Vila et al. (2003) noted that the patient had an unusually long survival time and suggested that mtDNA-depleted muscle fibers had become atrophic or died over time, while fibers with normal mtDNA had survived. Respiratory enzyme deficiency was attributed to accumulation of somatic mitochondrial mutations. In a study of skeletal muscle fibers from 2 sibs with mtDNA depletion myopathy due to TK2 mutations, who were previously reported by Mancuso et al. (2002), Durham et al. (2005) determined that muscle fiber mtDNA density of 0.01 mtDNA per cubic micrometer was the minimal amount of mtDNA required to maintain residual cytochrome c oxidase (COX) activity. Oskoui et al. (2006) reported 4 unrelated patients with the myopathic form of mtDNA depletion syndrome due to TK2 mutations. There was significant clinical variability: 1 patient had a rapidly progressive course with death at age 19 months, whereas the others showed a more protracted course. One died at age 6 years and another at age 16 years. The fourth child was alive at age 9 years and could walk independently with lumbar lordosis and toe walking. She had facial diplegia, decreased muscle mass, diffuse muscle weakness, and normal pulmonary function. Paradas et al. (2013) reported a 22-year-old man, born of consanguineous parents, with genetically confirmed MTDPS2 (T108M; 188250.0003) and a somewhat protracted course. He had normal development until age 24 months, when he showed proximal muscle weakness of the lower limbs resulting in a waddling gait. At age 20, he had a nasal voice and mild proximal arm weakness. After sudden onset of respiratory arrest triggered by pneumonia, he had rapid worsening of the muscle weakness and became wheelchair-bound. He had severe axial and proximal muscle weakness, facial weakness without ptosis, pectoral atrophy, scapular winging, and ankle contractures. He also had significant gynecomastia of unclear etiology. Laboratory studies showed increased serum creatine kinase and normal serum lactate. Muscle samples showed dystrophic features, endomysial fibrosis, abnormally shaped mitochondria, decreased mitochondrial complex I activity (35% of normal), and multiple mtDNA deletions (45% residual mtDNA). Family history revealed a 3-year-old sister who died of respiratory failure due to muscular dystrophy as well as 2 infant deaths in previous generations. The report was notable for significant intrafamilial phenotypic heterogeneity. ### Clinical Variability Behin et al. (2012) reported 3 unrelated patients with genetically confirmed MTDPS2 who had a milder course and slower progression than usually associated with this disorder. Although all patients reported some form of hypotonia, early fatigue, or delayed walking in early childhood and 2 had proximal muscle weakness in childhood, all presented in their early thirties with more significant impairment. Features included waddling gait, distal and proximal muscle weakness, axial weakness, and respiratory insufficiency. One patient was wheelchair-bound and 1 could not walk for more than 15 minutes. More variable features included ptosis, hypophonia, and facial weakness. Cognition, hearing, and cardiac function were normal in all patients. EMG showed a myogenic pattern, and muscle biopsies showed dystrophic changes consistent with a mitochondrial myopathy, including deficiencies of complexes I, III, and IV. Muscle mtDNA depletion was apparent, with mtDNA levels at about 30% of normal controls. This report expanded the phenotypic spectrum of MTDPS2 to include patients with much slower progression, which may have been due to better preservation of residual muscle mtDNA compared to more severely affected patients. However, there were no genotype/phenotype correlations, as 2 patients were homozygous for a previously reported mutation (T108M; 188250.0003) that had been observed in children with a more severe form of the disorder. Molecular Genetics In patients with the myopathic form of mtDNA depletion syndrome, Saada et al. (2001) identified mutations in the mitochondrial thymidine kinase gene, H90N and I181N, now H163N (188250.0001) and I254N (188250.0002), respectively. To further characterize the frequency and clinical spectrum of the causative mutations, Mancuso et al. (2002) screened 20 patients with myopathic mtDNA depletion syndrome. No patient had mutations in the deoxyguanosine kinase gene (DGUOK; 601465), but 4 patients from 2 families had TK2 mutations. Two sibs were compound heterozygotes for a previously reported H163N mutation (188250.0001) and a novel T77M mutation (now T150M; 188250.0003). Another pair of sibs harbored a homozygous I22M mutation (now I95M; 188250.0004), and 1 had evidence of lower motor neuron disease. Thus, the clinical expression of TK2 mutations is not limited to myopathy. The pathogenicity of these mutations was confirmed by reduced TK2 activity in muscle (28 to 37% of controls). In a family originally described by Tritschler et al. (1992) in which 3 sibs had myopathic mtDNA depletion syndrome, Mancuso et al. (2003) identified homozygosity for the T150M mutation. The patients had 80 to 90% mtDNA depletion in muscle biopsy specimens, and all died by age 40 months. The authors noted that exon 5 is a hotspot for TK2 mutations. Pathogenesis The human mitochondrial transcription factor A (TFAM; 600438) is a 25-kD protein that may be an important regulator of both transcription and replication of mtDNA. Deficiency of the yeast homolog, ABF2, is associated with loss of mtDNA. This prompted Poulton et al. (1994) to investigate both protein and mRNA levels for this factor in cell lines experimentally depleted of mtDNA and in patients with myopathic mtDNA depletion to determine whether these conditions are associated with a deficiency of TFAM. They found that the ratio of mtDNA to nuclear DNA in skeletal muscle was low in muscle from the 3 patients and in other tissues in 1. Furthermore, TFAM was low in cells depleted either permanently or transiently of mtDNA, and this reduction roughly paralleled mtDNA levels. They concluded that deficiency of TFAM may be a marker of, or possibly a cause of, mtDNA depletion in some patients with this condition. Wang et al. (2003) found that recombinant human TK2 with either the H163N (188250.0001) or the I254N (188250.0002) mutation, which they called H121N and I212N, respectively, had a similar subunit structure compared with wildtype TK2. The I212N mutant enzyme showed less than 1% activity compared with wildtype TK2 with all deoxynucleosides. The H121N mutant enzyme had normal Km values for thymidine and deoxycytidine, but 2- and 3-fold lower Vmax values, respectively, compared with wildtype TK2 and markedly increased Km values for ATP, leading to decreased enzyme efficiency. Competition experiments revealed that thymidine and deoxycytidine interacted differently with the H121N mutant compared with wildtype TK2. Animal Model Akman et al. (2008) created mice harboring a his126-to-asn (H126N) mutation in the Tk2 gene, which is homologous to the H163N mutation (188250.0001) in humans. Homozygous mutant mice (Tk2 -/-) were obtained at the expected mendelian frequency and appeared normal at birth. However, at postnatal day 10, they showed several defects relative to wildtype and heterozygous mutant littermates, including growth retardation, reduced spontaneous activity, generalized coarse tremor, and impaired gait. They rapidly developed weakness, leading to severe stress or death by 2 weeks of age. Tk2 -/- animals showed reduced Tk2 activity in all tissues analyzed, with activity reduced to 1.7% of wildtype in brain, the most severely affected tissue. In Tk2 -/- mice, brain mitochondria had a dTTP concentration about 20% of wildtype, and liver mitochondria showed reduced levels of both dTTP and dCTP. The content of other dNTPs in these tissues was unchanged, and dNTP levels in other tissues were not affected. Depletion of mtDNA was most prominent in brain, where it was 12.5% of wildtype, and only brain showed decreased activities of respiratory chain enzymes, primarily complexes I and IV, and reduced ATP levels and ATP/ADP ratios. Spinal cord neurons had abnormal vacuolar changes, and the white matter of spinal cord and cortex showed evidence of activated glial cells. Akman et al. (2008) concluded that, in contrast to the muscle-specific phenotype observed in patients with the H163N mutation, mice homozygous for the H126N mutation showed a rapidly progressive encephalomyelopathy. Bartesaghi et al. (2010) demonstrated that in vivo loss of Tk2 activity in mice led to a severe ataxic phenotype, accompanied by reduced mtDNA copy number and decreased steady-state levels of electron transport chain proteins in the brain. In Tk2-deficient cerebellar neurons, these abnormalities were associated with impaired mitochondrial bioenergetic function, aberrant mitochondrial ultrastructure, and degeneration of selected neuronal types. INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Facial diplegia RESPIRATORY \- Respiratory insufficiency due to muscle weakness MUSCLE, SOFT TISSUES \- Hypotonia \- Muscle weakness, proximal \- Gowers sign \- Muscle atrophy, diffuse \- Limb muscle weakness \- Delayed motor skills \- Inability to walk \- Loss of ability to walk in early childhood \- Myopathic changes seen on EMG \- Ragged red fibers seen on muscle biopsy \- Skeletal muscle tissue shows 14 to 45% depletion of mitochondrial DNA (mtDNA) \- Skeletal muscle may show less severe mtDNA deletion \- Decreased activities of mitochondrial-encoded respiratory chain complexes METABOLIC FEATURES \- Lactic acidosis LABORATORY ABNORMALITIES \- Increased serum creatine kinase \- Aminoaciduria MISCELLANEOUS \- Onset usually by age 2 years \- Later onset has been reported \- Variable severity \- Progressive disorder MOLECULAR BASIS \- Caused by mutation in the nuclear-encoded mitochondrial thymidine kinase gene (TK2, 188250.0001 ) ▲ 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	MITOCHONDRIAL DNA DEPLETION SYNDROME 2 (MYOPATHIC TYPE)	c3501891	3,968	omim	https://www.omim.org/entry/609560	2019-09-22T16:05:59	{"doid": ["0080120"], "mesh": ["C563698"], "omim": ["609560"], "orphanet": ["254875"], "synonyms": ["Alternative titles", "MITOCHONDRIAL DNA DEPLETION MYOPATHY, TK2-RELATED"], "genereviews": ["NBK114628"]}
The topic of this article may not meet Wikipedia's notability guideline for biographies. Please help to demonstrate the notability of the topic by citing reliable secondary sources that are independent of the topic and provide significant coverage of it beyond a mere trivial mention. If notability cannot be shown, the article is likely to be merged, redirected, or deleted. Find sources: "Joseph and Luka Banda" – news · newspapers · books · scholar · JSTOR (July 2018) (Learn how and when to remove this template message) Joseph and Luka Banda Born (1997-01-23) 23 January 1997 (age 23) Lusaka, Zambia Known forConjoined twins (1997－2001) Joseph Banda and Luka Banda (born 23 January 1997)[1] are twin brothers who used to be conjoined. They were born joined at the back of the skull and faced in opposite directions. In 1997, Ben Carson led a team of 50 Zambian and South African specialists to separate the 11-month-old twins in a 28-hour operation.[2] They did not share any organs, but shared intricate blood vessels that flowed into each other's brains. In 2001, the twins were fitted with artificial skulls to permanently close their heads, and are neurologically normal. In an interview, Carson stated about the operation: "In the end, the Bandas became the first Type 2 craniopagus twins (joined at the head and facing in opposite directions) ever separated with both surviving and both being neurologically normal."[3] However, a Zambia Daily Mail reporter revisiting the Bandas at 21 discovered Joseph had "mental challenges" that impeded his learning. He is described as "reclusive", and "not very responsive".[4] Luka dropped out of school in the ninth grade, and was often bullied due to the scars on his head. He is hoping to become a mechanic.[5] They are residing in an area of Lusaka called Chilenje South.[6] ## References[edit] 1. ^ Zambia: Zambian Siamese Twins Return Home Chibi Kubantu, Inter Press Service English News Wire 1998-04-09 (subscription required) 2. ^ "African separated twins offer hope for 'little Marias'". CNN.com. 2002-08-10. Retrieved 2015-10-22. 3. ^ Dreifus, Claudia (2000-01-04). "A CONVERSATION WITH - BENJAMIN S. CARSON - A Pioneer at a Frontier - The Brain of a Child". The New York Times. Retrieved 2015-05-29. 4. ^ "Luka, Joseph at 21 – Zambia Daily Mail". www.daily-mail.co.zm. Retrieved 2020-04-21. 5. ^ "Luka, Joseph at 21 – Zambia Daily Mail". www.daily-mail.co.zm. Retrieved 2020-04-21. 6. ^ "Luka, Joseph at 21 – Zambia Daily Mail". www.daily-mail.co.zm. Retrieved 2020-04-21. ## External links[edit] * BBC article - Joined at the head: medical briefing Monday, 9 April 2001 * Hopkins Medicine article * "Commencement 2000 - Ben Carson discussion of the operation This Zambian biographical 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	Joseph and Luka Banda	None	3,969	wikipedia	https://en.wikipedia.org/wiki/Joseph_and_Luka_Banda	2021-01-18T18:37:27	{"wikidata": ["Q6288169"]}
A rare ciliopathy characterized by oral anomalies (multiple oral frenula, missing incisors), facial dysmorphism (such as square face with small forehead, upslanting palpebral fissures, and cleft lip, among other features), digital anomalies (brachydactyly, brachymesophalangy, polydactyly), and short stature. Additional reported manifestations include short femoral neck, bilateral cervical ribs, abnormal vertebral bodies, and gracile long bones. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Oral-facial-digital syndrome with short stature and brachymesophalangy	c4693651	3,970	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=508501	2021-01-23T18:17:27	{"synonyms": ["OFD18", "Oral-facial-digital syndrome type 18", "Orofaciodigital syndrome type 18"]}
Cartilage-hair hypoplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities; fine, sparse hair (hypotrichosis); and abnormal immune system function (immune deficiency) that can lead to recurrent infections. People with cartilage-hair hypoplasia have unusually short limbs and short stature from birth. They typically have malformations in the cartilage near the ends of the long bones in the arms and legs (metaphyseal chondrodysplasia), which then affects development of the bone itself. Most people with cartilage-hair hypoplasia are unusually flexible in some joints, but they may have difficulty extending their elbows fully. Affected individuals have hair that is lighter in color than that of other family members because the core of each hair, which contains some of the pigment that contributes the hair's color, is missing. The missing core also makes each strand of hair thinner, causing the hair to have a sparse appearance overall. Unusually light-colored skin (hypopigmentation), malformed nails, and dental abnormalities may also be seen in this disorder. The extent of the immune deficiency in cartilage-hair hypoplasia varies from mild to severe. Affected individuals with the most severe immune problems are considered to have severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from bacteria, viruses, and fungi and are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by "opportunistic" organisms that ordinarily do not cause illness in people with a normal immune system. Most people with cartilage-hair hypoplasia, even those who have milder immune deficiency, experience infections of the respiratory system, ears, and sinuses. In particular, the chicken pox virus (varicella) often causes dangerous infections in people with this disorder. Autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs, occur in some people with cartilage-hair hypoplasia. Affected individuals are also at an increased risk of developing cancer, particularly certain skin cancers (basal cell carcinomas), cancer of blood-forming cells (leukemia), and cancer of immune system cells (lymphoma). Some people with cartilage-hair hypoplasia experience gastrointestinal problems. These problems may include an inability to properly absorb nutrients or intolerance of a protein called gluten found in wheat and other grains (celiac disease). Affected individuals may have Hirschsprung disease, an intestinal disorder that causes severe constipation, intestinal blockage, and enlargement of the colon. Narrowing of the anus (anal stenosis) or blockage of the esophagus (esophageal atresia) may also occur. ## Frequency Cartilage-hair hypoplasia occurs most often in the Old Order Amish population, where it affects about 1 in 1,300 newborns. In people of Finnish descent, its incidence is approximately 1 in 20,000. Outside of these populations, the condition is rare, and its specific incidence is not known. It has been reported in individuals of European and Japanese descent. ## Causes Cartilage-hair hypoplasia is caused by mutations in the RMRP gene. Unlike many genes, the RMRP gene does not contain instructions for making a protein. Instead, a molecule called a noncoding RNA, a chemical cousin of DNA, is produced from the RMRP gene. This RNA attaches (binds) to several proteins, forming an enzyme complex called mitochondrial RNA-processing endoribonuclease, or RNase MRP. The RNase MRP enzyme is thought to be involved in several important processes in the cell. For example, it likely helps copy (replicate) the DNA found in the energy-producing centers of cells (mitochondria). The RNase MRP enzyme probably also processes ribosomal RNA, which is required for assembling protein building blocks (amino acids) into functioning proteins. In addition, this enzyme helps control the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion. Mutations in the RMRP gene likely result in the production of a noncoding RNA that is unstable. This unstable molecule cannot bind to some of the proteins needed to make the RNase MRP enzyme complex. These changes are believed to affect the activity of the enzyme, which interferes with its important functions within cells. Disruption of the RNase MRP enzyme complex causes the signs and symptoms of cartilage-hair hypoplasia. ### Learn more about the gene associated with Cartilage-hair hypoplasia * RMRP ## Inheritance Pattern This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Cartilage-hair hypoplasia	c0220748	3,971	medlineplus	https://medlineplus.gov/genetics/condition/cartilage-hair-hypoplasia/	2021-01-27T08:25:09	{"gard": ["6996"], "mesh": ["C535916"], "omim": ["250250"], "synonyms": []}
A rare, genetic primary bone dysplasia of the spondylo-epi-metaphyseal dysplasia (SEMD) group characterized by progressive short-trunked dwarfism, protruding sternum, microcephaly, intellectual disability and pathognomonic radiological findings (generalized platyspondyly with double-humped end plates, irregularly ossified femoral heads, a hypoplastic odontoid, and a lace-like appearance of iliac crests) ## Epidemiology To date approximately 100 cases have been reported worldwide. ## Clinical description Clinically, Dyggve-Melchior-Clausen disease (DMC) is characterized by progressive dwarfism with short trunk, protruding sternum, rhizomelic limb shortening, postnatal microcephaly with facial dysmorphism, coarse face and intellectual disability varying from moderate to severe. Physical measurements at birth are typically normal, with patients clinically presenting with short stature within the first two years of life along with progressive appearance of the skeletal deformities of the thorax, spine, pelvis, hands and knees. Orthopedic complications usually occur during childhood almost constantly including bilateral hip subluxation, deformations of the knees, lumbar lordosis, scoliosis and thoracic kyphosis. Radiological features include progressive flattened vertebral bodies (platyspondyly) with a double-humped shape clearly visible by 3-4 years of age, misaligned spine, metaphyseal irregularities, laterally displaced capital femoral epiphyses, and small pelvis with thickened and scalloped iliac crests. This specific aspect of iliac crests becomes clearly visible around 4 years of age, broadens through adolescence and persists into adulthood. Hands are generally short and broad with irregular shape of metacarpal bones and phalanges. ## Etiology The disease is caused by mutations of the DYM gene (18q21.1). The large majority of mutations identified in the gene predict a loss of function of its product. DYM is expressed in the majority of tissue and codes for dymeclin, a protein which interacts with membranes of the Golgi apparatus, and has a role in the regulation of Golgi homeostasis and membrane trafficking ## Diagnostic methods Diagnosis is based on radiological evidence revealing platyspondyly with double vertebral humps, epiphyseal and metaphyseal dysplasia and scalloped iliac crests. ## Differential diagnosis Differential diagnoses include Smith-McCort syndrome, which presents with the same clinical and radiological features as DMC but without intellectual deficiency, and mucopolysaccharidosis type 4 which is clinically similar but has specific radiological and enzymatic signs. ## Genetic counseling Transmission is autosomal recessive. There is a 25% risk of disease transmission where both parents are unaffected carriers. ## Management and treatment Management requires both a multidisciplinary approach and a long-term follow-up as the disease is progressive. Preventive or corrective orthopedic surgery may be an option to manage lower limb deformities. However, due to the poor quality of osseous tissue, minimal-invasive surgery such as guided growth may be preferable ## Prognosis The disease often progresses towards orthopedic complications which can include lumbar lordosis, thoracic kyphosis, hip luxation, deformation of the knees and spinal cord compression secondary to instability of the atlas-axis. * European Reference Network [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Dyggve-Melchior-Clausen disease	c0265286	3,972	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=239	2021-01-23T17:45:31	{"gard": ["6295"], "mesh": ["C535726"], "omim": ["223800", "304950"], "umls": ["C0265286"], "icd-10": ["Q77.7"]}
Pretibial dystrophic epidermolysis bullosa is a rare subtype of dystrophic epidermolysis bullosa (DEB, see this term) characterized by the development of blisters, erosions, and lichenoid lesions predominantly in the pretibial region. ## Epidemiology Prevalence is unknown. Approximately 40 families or sporadic cases have been reported to date. ## Clinical description The disease usually manifests at birth or during infancy, but may also be delayed until the adolescence. It involves almost exclusively the anterior lower legs (pretibial areas and feet), the hands and nails. Individual lesions, which tend to be papular or plaque-like, are often violaceous, suggesting the clinical diagnosis of lichen planus. Some patients complain of pruritus. Healing of blisters is associated with hypertrophic scarring and milia formation. Dystrophy of both fingernails and toenails is characteristic. Unlike in lichen planus, these nail changes do not include pterygium formation. ## Etiology Pretibial DEB is caused by mutations within the type VII collagen gene (COL7A1). Mutations in this gene lead to an alteration of function or to reduced amounts of collagen VII. This impairs collagen VII assembly into anchoring fibrils which anchor the basement membrane to the underlying dermis. This in turn causes reduced skin resistance to minor trauma. ## Genetic counseling The disease follows an autosomal dominant (pretibial DDEB) or an autosomal recessive (pretibial RDEB) pattern of inheritance. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Pretibial dystrophic epidermolysis bullosa	c0432321	3,973	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79410	2021-01-23T18:58:13	{"gard": ["2155"], "mesh": ["C535494"], "omim": ["131850"], "umls": ["C0432321"], "icd-10": ["Q81.2"], "synonyms": ["DEB-Pt", "Pretibial DEB"]}
Chronic granulomatous disease is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body from foreign invaders such as bacteria and fungi. Individuals with chronic granulomatous disease may have recurrent bacterial and fungal infections. People with this condition may also have areas of inflammation (granulomas) in various tissues that can result in damage to those tissues. The features of chronic granulomatous disease usually first appear in childhood, although some individuals do not show symptoms until later in life. People with chronic granulomatous disease typically have at least one serious bacterial or fungal infection every 3 to 4 years. The lungs are the most frequent area of infection; pneumonia is a common feature of this condition. Individuals with chronic granulomatous disease may develop a type of fungal pneumonia, called mulch pneumonitis, which causes fever and shortness of breath after exposure to decaying organic materials such as mulch, hay, or dead leaves. Exposure to these organic materials and the numerous fungi involved in their decomposition causes people with chronic granulomatous disease to develop fungal infections in their lungs. Other common areas of infection in people with chronic granulomatous disease include the skin, liver, and lymph nodes. Inflammation can occur in many different areas of the body in people with chronic granulomatous disease. Most commonly, granulomas occur in the gastrointestinal tract and the genitourinary tract. In many cases the intestinal wall is inflamed, causing a form of inflammatory bowel disease that varies in severity but can lead to stomach pain, diarrhea, bloody stool, nausea, and vomiting. Other common areas of inflammation in people with chronic granulomatous disease include the stomach, colon, and rectum, as well as the mouth, throat, and skin. Additionally, granulomas within the gastrointestinal tract can lead to tissue breakdown and pus production (abscesses). Inflammation in the stomach can prevent food from passing through to the intestines (gastric outlet obstruction), leading to an inability to digest food. These digestive problems cause vomiting after eating and weight loss. In the genitourinary tract, inflammation can occur in the kidneys and bladder. Inflammation of the lymph nodes (lymphadenitis) and bone marrow (osteomyelitis), which both produce immune cells, can lead to further impairment of the immune system. Rarely, people with chronic granulomatous disease develop autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs. Repeated episodes of infection and inflammation reduce the life expectancy of individuals with chronic granulomatous disease; however, with treatment, most affected individuals live into mid- to late adulthood. ## Frequency Chronic granulomatous disease is estimated to occur in 1 in 200,000 to 250,000 people worldwide. ## Causes Mutations in the CYBA, CYBB, NCF1, NCF2, or NCF4 gene can cause chronic granulomatous disease. There are five types of this condition that are distinguished by the gene that is involved. The proteins produced from the affected genes are parts (subunits) of an enzyme complex called NADPH oxidase, which plays an essential role in the immune system. Specifically, NADPH oxidase is primarily active in immune system cells called phagocytes. These cells catch and destroy foreign invaders such as bacteria and fungi. Within phagocytes, NADPH oxidase is involved in the production of a toxic molecule called superoxide. Superoxide is used to generate other toxic substances, which play a role in killing foreign invaders and preventing them from reproducing in the body and causing illness. NADPH oxidase is also thought to regulate the activity of immune cells called neutrophils. These cells play a role in adjusting the inflammatory response to optimize healing and reduce injury to the body. Mutations in the CYBA, CYBB, NCF1, NCF2, and NCF4 genes result in the production of proteins with little or no function or the production of no protein at all. Mutations in the genes that cause chronic granulomatous disease that prevent the production of any functional protein are designated "0". For example, mutations in the CYBB gene that lead to no functional beta chain are designated CYBB0. Mutations that lead to a reduction of the amount of protein produced are designated "-", for example, CYBB-. Without any one of its subunit proteins, NADPH oxidase cannot assemble or function properly. As a result, phagocytes are unable to kill foreign invaders and neutrophil activity is not regulated. A lack of NADPH oxidase leaves affected individuals vulnerable to many types of infection and excessive inflammation. Some people with chronic granulomatous disease do not have an identified mutation in any of these genes. The cause of the condition in these individuals is unknown. ### Learn more about the genes associated with Chronic granulomatous disease * CYBA * CYBB * NCF1 * NCF2 * NCF4 ## Inheritance Pattern When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. The CYBB gene 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. Rarely, females with one altered copy of the CYBB gene have mild symptoms of chronic granulomatous disease, such as an increased frequency of bacterial or fungal infections. When chronic granulomatous disease is caused by CYBA, NCF1, NCF2, or NCF4 gene mutations, the 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. Men and women are affected by autosomal recessive conditions equally. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Chronic granulomatous disease	c1856251	3,974	medlineplus	https://medlineplus.gov/genetics/condition/chronic-granulomatous-disease/	2021-01-27T08:25:06	{"gard": ["6100"], "mesh": ["C565532"], "omim": ["233700", "233710", "613960", "233690", "306400"], "synonyms": []}
A number sign (#) is used with this entry because hyperlipoproteinemia type ID is caused by homozygous or compound heterozygous mutation in the GPIHBP1 gene (612757) on chromosome 8q24. Clinical Features Wang and Hegele (2007) reported 2 sibs with chylomicronemia who were found to have a homozygous mutation in the GPIHBP1 gene. The female had relapsing pancreatitis beginning at age 22 and documented on numerous occasions to have refractory fasting chylomicronemia, even with fat restriction. She had no thyroid, renal, or hepatic disease and was not diabetic. She was not obese and consumed no alcohol. Her older brother had a similar biochemical profile, with a history of pancreatitis requiring hospitalization, refractory to medical treatment since age 25. At age 45, he required 3-vessel coronary artery bypass graft surgery for unstable angina symptoms that began at age 44. Three heterozygotes in this pedigree had plasma triglyceride concentrations in the top 5th percentile for age and sex, but no history of pancreatic or cardiovascular disease. Beigneux et al. (2009) reported a 33-year-old male with chylomicronemia. The patient was born in Colombia and adopted by a Dutch family. As a child, he exhibited hepatosplenomegaly and failure to thrive; he was diagnosed with type I hyperlipoproteinemia at the age of 7 years. He had a normal BMI of 24.4 and normal glucose levels. Fasting chylomicronemia was documented on multiple occasions. The hyperlipidemia was partially responsive to diet; fasting plasma triglyceride levels fell from as high as 3,366 mg/dL to as low as 744 mg/dL when the patient adhered to a fat-free diet. He had had lipemia retinalis but had no history of eruptive xanthomas or pancreatitis. Olivecrona et al. (2010) reported a family from northern Sweden in which 3 of 4 sibs had congenital chylomicronemia. Lipoprotein lipase (LPL; 609708) activity and mass in pre- and postheparin plasma were low, and LPL release into plasma after heparin injection was delayed. LPL activity and mass in adipose tissue biopsies appeared normal. Breast milk from the affected female subjects contained normal to elevated LPL mass and activity levels. The milk had a lower than normal milk lipid content, and the fatty acid composition was compatible with the milk lipids derived from de novo lipogenesis, rather than from the plasma lipoproteins. In addition to chylomicronemia, the proband had hepatosplenomegaly, for which she was referred to a pediatric clinic at 9 months of age. Blood sampling revealed lipemic serum, and she developed abdominal pain early in life. She tolerated 1 pregnancy by reducing dietary fat to less than 15% of caloric intake. During subsequent pregnancies, however, she underwent prophylactic plasmaphereses during the second and third trimesters. Her brother was diagnosed at 10 years of age due to fatigue and lipemic serum. He had never been ill or had any episodes of abdominal pain, but he did have mild splenomegaly on physical examination. The proband's sister had severe hypertriglyceridemia and chylomicronemia as well as episodes of pancreatitis. Franssen et al. (2010) reported a boy with severe chylomicronemia who was diagnosed at 1 year of age during a bout of pancreatitis. Fasting plasma triglyceride levels were 4,005 mg/dL. His weight was less than the 10th percentile for his age, and funduscopy revealed lipemia retinalis; however, he had neither hepatosplenomegaly nor eruptive xanthomas. The patient's hyperlipidemia was partially responsive to a low-fat diet, which caused his plasma triglyceride level to drop from approximately 4,000 to 1,575 mg/dL. His parents and his 3 sibs were healthy, with normal plasma lipid and apolipoprotein levels. Charriere et al. (2011) reported 2 patients with hyperchylomicronemia. One patient was a 35-year-old man who had been referred at age 26 years for severe acute pancreatitis with hyperchylomicronemia (triglycerides, 26 mmol/L). He remained mostly hyperchylomicronemic with recurrent acute pancreatitis. His LPL activity was undetectable; his mother and daughter had normal lipid parameters. The other patient was a young child who was diagnosed with hyperchylomicronemia at 6 months of age during an episode of acute pancreatitis (triglycerides, 19.6 mmol/L). During childhood, triglycerides remained moderately increased under strict diet, with several episodes of hyperchylomicronemia but without recurrence of acute pancreatitis. His LPL activity was undetectable; both parents and his younger brother had normal lipid profiles. Gonzaga-Jauregui et al. (2014) reported a 5-week-old Hispanic girl who presented with severe hypertriglyceridemia (triglycerides, 12,031 mg/dL) and a combination of lower gastrointestinal bleeding and chylomicronemia. Initial colonoscopy was consistent with colitis, which resolved with reduction of triglycerides. She had a low HDL of 11 mg/dL and reduced LPL activity. Plengpanich et al. (2014) reported 3 sibs with chylomicronemia. Their plasma triglycerides ranged from 673 to 3,164 mg/dL, and HDL cholesterol was lowered to 16, 32, and 13, respectively. The proband was identified at 40 years of age after presenting with epigastric discomfort and a plasma triglyceride level of 2,050 mg/dL. Her BMI was normal, and her fasting plasma triglyceride level at 46 years of age was 3,164 mg/dL. Fasting glucose and thyroid-stimulating hormone levels were normal. She had no eruptive xanthomas, and reported 2 uneventful pregnancies. Two of her brothers had a history of chylomicronemia but had lower plasma triglyceride levels than the proband. The preheparin plasma LPL levels in the 3 affected sibs were much lower than those in other family members. The postheparin plasma levels in the proband were extremely low (127 ng/mL), less than 5% of those in normolipidemic control subjects. Molecular Genetics Wang and Hegele (2007) screened the coding regions of the GPIHBP1 gene in 160 unrelated adults with fasting chylomicronemia and plasma triglycerides greater than 10 mmol/L, each of whom had normal sequence of the LPL (609708) and APOC2 (608083) genes and identified 1 patient who was homozygous for a missense mutation (G56R; 612757.0001). Her affected brother was homozygous for the same mutation. Both sibs had recurrent pancreatitis. Functional studies by Gin et al. (2007) called into question the pathogenicity of this variant. In a 33-year-old man with hyperlipoproteinemia type I since childhood, Beigneux et al. (2009) identified homozygosity for a missense mutation in the GPIHBP1 gene (Q115P; 612757.0002). The same homozygous mutation was found in an unrelated patient with severe hypertriglyceridemia by Surendran et al. (2012). In a 3-year-old boy with chylomicronemia, Franssen et al. (2010) identified homozygosity for a missense mutation in the GPIHBP1 gene (C65Y; 612757.0009), which was subsequently reported in homozygosity in an unrelated patient by Surendran et al. (2012). In 3 Swedish sibs with severe chylomicronemia, Olivecrona et al. (2010) identified compound heterozygous mutations in the GPIHBP1 gene (C65S, 612757.0003 and C68G, 612757.0004). In a 35-year-old man with severe chylomicronemia, Charriere et al. (2011) identified a homozygous missense mutation in the GPIHBP1 gene (G175R; 612757.0005). In a child with the same disorder, they identified compound heterozygosity for a missense mutation (C89F; 612757.0006) inherited from the father and a deletion of GPIHBP1 (612757.0011) inherited from the mother. Charriere et al. (2011) suggested that a signal peptide polymorphism (C14F) that occurred in cis with the C89F variant may have potentiated the effect of C89F, which caused a drastic LPL-binding defect to GPIHBP1. In a 5-week-old Hispanic girl with severe hypertriglyceridemia, Gonzaga-Jauregui et al. (2014) identified compound heterozygosity for a missense (T111P; 612757.0007) and a frameshift (612757.0008) mutation in the GPIHBP1 gene. In 3 sibs with hypertriglyceridemia, Plengpanich et al. (2014) identified homozygosity for a missense mutation in the GPIHBP1 gene (S107C; 612757.0010). Pathogenesis Franssen et al. (2010) studied the patient with chylomicronemia reported by Beigneux et al. (2009) with a Q115P mutation in the GPIHBP1 gene (612757.0002). When this patient was given a 6-hour infusion of heparin, a significant amount of LPL appeared in the plasma, resulting in a fall in the plasma triglyceride levels from 1,780 to 120 mg/dL. INHERITANCE \- Autosomal recessive GROWTH Weight \- Low body weight (< 10th centile) Other \- Failure to thrive HEAD & NECK Eyes \- Lipemia retinalis (in some patients) ABDOMEN Liver \- Hepatomegaly (reported in pediatric cases) Pancreas \- Pancreatitis, relapsing (in most patients) Spleen \- Splenomegaly (reported in pediatric cases) Gastrointestinal \- Colitis (rare) SKIN, NAILS, & HAIR Skin \- Facial xanthomatous eruptions (rare) LABORATORY ABNORMALITIES \- Type I hyperlipoproteinemia \- High plasma triglyceride levels \- Chylomicronemia, refractory fasting \- Decreased plasma LPL levels (in some patients) \- High-normal plasma triglyceride concentration (in heterozygotes) MISCELLANEOUS \- Hyperlipidemia may be partially responsive to fat-restricted diet MOLECULAR BASIS \- Caused by mutation in the glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 gene (GPIHBP1, 612757.0002 ) ▲ Close [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	HYPERLIPOPROTEINEMIA, TYPE ID	c4014767	3,975	omim	https://www.omim.org/entry/615947	2019-09-22T15:50:30	{"omim": ["615947"], "orphanet": ["444490", "535458"], "synonyms": ["Familial glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 deficiency"]}
A number sign (#) is used with this entry because of evidence that spermatogenic failure-10 (SPGF10) is caused by heterozygous mutation in the SEPT12 gene (611562) on chromosome 16p13. Description Spermatogenic failure-10 is associated with a defective annulus, a ring structure that demarcates the midpiece and the principal piece of the sperm tail. The firm attachment of the annulus to the flagellar membrane suggests that it may supply mechanical support and prevent displacement of the caudal mitochondrial helix (summary by Kuo et al., 2012). For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). Clinical Features Kuo et al. (2012) studied 2 infertile men with SEPT12 mutations. The first man had asthenoteratozoospermia, with a sperm count of 20.5 x 10(6)/ml, morphology that was 92% abnormal, and a total motility of 48% (42% rapid progressive motility, 6% slow progressive motility, and 52% nonprogressive motility). The second man had oligoasthenozoospermia, with a sperm count of 0.9 x 10(6)/ml, morphology that was 80% abnormal, and a total motility of 22% (consisting of 22% slow progressive motility and 78% nonprogressive motility; no rapid progressive motility was seen in this patient's sperm). Atomic force microscopy of the second man's sperm detected loss of the annular structure and a bent tail, as well as outward exposure of the flagellar axoneme. The height of the annulus site was about 20 to 40 nm, significantly lower than in a control (160 nm). Under bright-field and fluorescence microscopy, the sperm had multiple defects; transmission electron microscopy showed noncondensed chromatin material, cytoplasmic droplets, a shrunken joining point with minimal connection, and a bent tail. Molecular Genetics Lin et al. (2012) analyzed the SEPT12 gene (611562) in 160 infertile men and 200 fertile controls and identified a variant (474G-A; 611562.0001) that was more prevalent in infertile men than controls, in both allele (p = 0.007) and genotype (p = 0.003) frequencies. Of 15 infertile men who were homozygous for the SNP (474A/A), 9 had teratozoospermia (88 to 99% of abnormal sperm). Motile sperm organelle morphology examination and immunofluorescence assay showed that most sperm had distinct pathologic features, including a bent tail, head with abnormal shape, and immature spermatid. Transfection studies showed that the mutant SEPT12 disrupted filament formation of wildtype SEPT12 in a dose-dependent manner. Examination of sperm from 474A/A infertile men by transmission electron microscopy showed a loose nuclear matrix; narrow head and decondensed nuclear matrix was observed under atomic force microscopy. Kuo et al. (2012) analyzed the SEPT12 gene in 160 infertile men and identified 2 heterozygous missense mutations, 1 in a man with asthenoteratozoospermia and 1 in a man with oligoasthenozoospermia (611562.0002, 611562.0003). Functional analysis demonstrated that both mutations adversely affected filament formation of wildtype SEPT12 in a dose-dependent manner. INHERITANCE \- Autosomal dominant GENITOURINARY Internal Genitalia (Male) \- Infertility \- Spermatogenic failure \- Teratozoospermia (in some patients) \- Asthenoteratozoospermia (in some patients) \- Oligoasthenozoospermia (in some patients) MOLECULAR BASIS \- Caused by mutation in the septin 12 gene (SEPT12, 611562.0001 ) ▲ 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	SPERMATOGENIC FAILURE 10	c3553793	3,976	omim	https://www.omim.org/entry/614822	2019-09-22T15:54:16	{"doid": ["0070178"], "omim": ["614822"], "orphanet": ["276234"], "synonyms": ["SPERMATOGENIC FAILURE WITH DEFECTIVE SPERM ANNULUS", "Alternative titles", "Non-syndromic male infertility due asthenozoospermia"]}
## Description The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). For a discussion of genetic heterogeneity of neuronal ceroid lipofuscinosis, see CLN1 (256730). Clinical Features Schulz et al. (2004) described a ninth variant of juvenile-onset neuronal ceroid lipofuscinosis in 2 Serbian sisters and 2 German brothers. The sisters, whose great-grandmothers came from adjacent villages, developed declining vision, progressive ataxia, and seizures by age 4 years. By age 10 years, they could not walk independently and became mute. The 2 brothers showed a similar course as the sisters, presenting at age 4 years with declining vision and seizures. Cognitive decline was apparent at age 6 years, ataxia and rigidity occurred at age 9 years, and they were mute by age 12 years. The younger brother died at age 15 years following pneumonia, and the older brother, who later had hallucinations and dysphagia, died at age 19 years. All patients had slowed EEGs with polyspike wave discharges. Laboratory studies in 1 of the brothers showed neurons ballooned with autofluorescent fine granular material. A brain biopsy from 1 sister showed neurons with granular and curvilinear bodies. Fibroblasts from all patients were small and rounded with prominent nucleoli, attached poorly, and were highly apoptotic. They showed increased DNA synthesis and increased expression of several cyclins. Patient fibroblasts also showed a decrease in ceramide, sphingomyelin, lactosylceramide, ceramide trihexoside, and globoside, indicating a perturbation of sphingolipid metabolism. Enzyme screening and genetic testing ruled out other NCL types and lysosomal storage disorders. Schulz et al. (2006) found that fibroblasts derived from patients with neuronal ceroid lipofuscinosis-9 showed markedly decreased levels of dihydroceramide and decreased dihydroceramide synthase activity. The cells showed partial correction of growth defects and apoptosis when transfected with CLN8 (607837) and several human LASS genes (see, e.g., LASS1; 606919), all of which increase dihydroceramide synthase activity. Schulz et al. (2006) concluded that the CLN9 protein may be a regulator of dihydroceramide synthase. Inheritance The transmission pattern of CLN9 in the families reported by Schulz et al. (2004) was consistent with autosomal recessive inheritance. Molecular Genetics In affected sibs from 1 of the families reported by Schulz et al. (2004), El Haddad et al (2012) identified a homozygous nonsense mutation in the CLN5 gene (Q232X; 608102.0010). The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. This family was thus reclassified as having neuronal ceroid lipofuscinosis-5 (CLN5; 256731). The same region of homozygosity on chromosome 13 was found uniquely in probands of the second family; however, exon and promoter sequencing in the second family did not reveal mutations in the CLN5 gene, suggesting that the mutation is probably intronic or in a different gene altogether. INHERITANCE \- Autosomal recessive HEAD & NECK Eyes \- Vision loss, progressive (4 to 10 years) \- Retinitis pigmentosa \- Optic atrophy \- Decreased electroretinogram (ERG) NEUROLOGIC Central Nervous System \- Psychomotor degeneration \- Mental retardation \- Seizures \- Ataxia \- Rigidity \- Progressive inability to walk \- Dysarthria \- Scanning speech \- Mutism \- Cerebral atrophy \- EEG is slowed with polyspike wave discharges \- 'Ballooned' neurons with autofluorescent fine granular material \- Apoptotic neurons HEMATOLOGY \- Vacuolated lymphocytes LABORATORY ABNORMALITIES \- Fibroblasts are small and rounded with prominent nucleoli \- Fibroblasts attach poorly \- Fibroblasts show increased sensitivity to apoptosis \- Fibroblasts demonstrate rapid growth with increased DNA synthesis \- 'Fingerprint profiles' ultrastructurally in cells \- 'Curvilinear profiles' ultrastructurally in cells \- Fibroblasts have decreased levels of ceramide, sphingomyelin, lactosylceramide, ceramide trihexoside, and globoside \- Fibroblasts have increased activity of serine palmitoyltransferase (SPT, 605712 ) MISCELLANEOUS \- One family has been reported (last curated March 2016) \- Onset at 4 years of age \- Early death \- Similar phenotype to juvenile neuronal ceroid lipofuscinosis 3 (CLN3, 204200 ) ▲ 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	CEROID LIPOFUSCINOSIS, NEURONAL, 9	c1836841	3,977	omim	https://www.omim.org/entry/609055	2019-09-22T16:06:48	{"doid": ["0110733"], "mesh": ["C537953"], "omim": ["609055"], "orphanet": ["228357", "79264"]}
Thyroid lymphoma SpecialtyENT surgery, endocrinology, oncology Thyroid lymphoma is a rare cancer constituting 1% to 2% of all thyroid cancers and less than 2% of lymphomas. Thyroid lymphomas are classified as non–Hodgkin's B-cell lymphomas in a majority of cases, although Hodgkin's lymphoma of the thyroid has also been identified.[1] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 2.1 Histopathology * 2.2 Staging * 3 Treatment * 4 Prognosis * 5 References * 6 External links ## Signs and symptoms[edit] As with other thyroid lesions, thyroid lymphoma affects predominantly females over 70 years of age with a history of Hashimoto's thyroiditis. Thus, Hashimoto's thyroiditis is considered a risk factor for thyroid lymphoma development. Thyroid lymphoma manifests as a rapidly enlarging neck mass which may compress the nearby trachea thereby causing narrowing or obstruction of the airway resulting in breathing difficulties or even respiratory failure. On physical examination, affected people typically exhibit a firm thyroid gland and enlarged lymph nodes. * Painless neck mass * Hoarseness * Difficulty swallowing * Signs of tracheal compression ## Diagnosis[edit] Thyroid lymphoma poses a diagnostic and therapeutic challenge. This is because several manifestation patterns are similar to those of anaplastic thyroid cancer (ATC). Fine-needle aspiration (FNA) helps distinguish the two entities preoperatively. ### Histopathology[edit] The majority of thyroid lymphomas are non–Hodgkin's B-cell lymphomas; a minority exhibit properties of T-cell lymphomas . * Diffuse large B-cell lymphoma with marginal zone * Diffuse large B-cell lymphoma without marginal zone * Marginal zone В-cell lymphoma of mucosa-associated lymphoid tissue (MALT) * Follicular lymphoma ### Staging[edit] Staging of thyroid lymphoma is shown in the table below Stage Characteristics 1Е Lymphoma is located within the thyroid 2Е Lymphoma is located within the thyroid and regional lymph-nodes 3Е Lymphoma is located at both sides of diaphragm 4Е Dissemination of lymphoma ## Treatment[edit] Combined modality therapy is the most common approach for the initial treatment of thyroid lymphomas. The CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) has been shown to be highly effective for many types of thyroid lymphoma.[medical citation needed] However, it is suggested to perform radiation therapy only for MALT resulting a 96% complete response, with only a 30% relapse rate. Surgical treatment might be performed for patients with thyroid lymphoma in addition to chemotherapy and radiation, particularly for MALT lymphomas. ## Prognosis[edit] The factors of poor prognosis for people with thyroid lymphoma are advanced stage of the tumor, large size (>10 cm) as well as spreading to mediastinum. The overall survival for primary thyroid lymphoma is 50% to 70%, ranging from 80% in stage IE to less than 36% in stage IIE and IVE in 5 years. ## References[edit] 1. ^ Sakorafas GH, Kokkoris P, Farley DR (2010). "Primary thyroid lymphoma (correction of lympoma): diagnostic and therapeutic dilemmas". Surg Oncol. 19 (4): 124–29. doi:10.1016/j.suronc.2010.06.002. PMID 20620043. ## External links[edit] Classification D * ICD-10: C73, C81-C96 * ICD-9-CM: 193 * MeSH: D013964 * v * t * e Tumours of endocrine glands Pancreas * Pancreatic cancer * Pancreatic neuroendocrine tumor * α: Glucagonoma * β: Insulinoma * δ: Somatostatinoma * G: Gastrinoma * VIPoma Pituitary * Pituitary adenoma: Prolactinoma * ACTH-secreting pituitary adenoma * GH-secreting pituitary adenoma * Craniopharyngioma * Pituicytoma Thyroid * Thyroid cancer (malignant): epithelial-cell carcinoma * Papillary * Follicular/Hurthle cell * Parafollicular cell * Medullary * Anaplastic * Lymphoma * Squamous-cell carcinoma * Benign * Thyroid adenoma * Struma ovarii Adrenal tumor * Cortex * Adrenocortical adenoma * Adrenocortical carcinoma * Medulla * Pheochromocytoma * Neuroblastoma * Paraganglioma Parathyroid * Parathyroid neoplasm * Adenoma * Carcinoma Pineal gland * Pinealoma * Pinealoblastoma * Pineocytoma MEN * 1 * 2A * 2B [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: 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 lymphoma	c1336753	3,978	wikipedia	https://en.wikipedia.org/wiki/Thyroid_lymphoma	2021-01-18T19:08:02	{"umls": ["C1336753"], "icd-9": ["193"], "icd-10": ["C96", "C73", "C81"], "orphanet": ["97285"], "wikidata": ["Q3832897"]}
Carney et al. (1980) suggested that pheochromocytoma and/or islet cell tumor is an autosomal dominant endocrine adenomatosis distinct from MEA I, II and III. They reported 3 families. Among 11 affected patients (aged 5 to 53 years), 10 had pheochromocytoma (bilateral in 6), 4 had islet cell tumor (multicentric in 1), and 3 had both tumors. Clinical presentation was due to pheochromocytoma in 10 (symptoms or signs beginning before age 10 years in 3) and islet cell tumor in 1. Two patients died from pheochromocytoma and 2 from islet cell carcinoma. One of their probands had numerous cafe-au-lait spots up to 4 cm in diameter and axillary freckling. There was, however, no family history of von Recklinghausen disease. Most of the other families in the literature with this combination of endocrine tumors had von Hippel-Lindau disease (VHL; 193300). For example, Hull et al. (1979) reported sibs with VHL syndrome who had both pheochromocytoma and islet cell adenomas. Thus, the case for a separate pheochromocytoma-islet cell tumor cannot be considered proved. Zeller et al. (1982) reported the eleventh case of this association. Endocrine \- Episodic hypertension Oncology \- Pheochromocytoma \- Islet cell tumor Neuro \- Cerebral hemorrhage Skin \- Cafe-au-lait spots \- Axillary freckling \- Sweating Cardiac \- Tachycardia \- Congestive heart failure Inheritance \- Autosomal dominant \- ? same as von Hippel-Lindau disease Misc \- Familial pheochromocytoma usually bilateral Eyes \- Hypertensive retinopathy Lab \- Proteinuria \- Hypercalcemia \- Positive Regitine test \- Elevated urinary norepinephrine ▲ 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	PHEOCHROMOCYTOMA--ISLET CELL TUMOR SYNDROME	c1868392	3,979	omim	https://www.omim.org/entry/171420	2019-09-22T16:36:18	{"mesh": ["C566807"], "omim": ["171420"]}
On the island of Rodrigues in the Indian Ocean, Wallis and Beighton (1992) identified a brother and sister with moderately severe mental retardation, blindness due to severe ocular malformations (microphthalmia, microcornea, and sclerocornea), short stature, dysmorphic facial features (narrow nasal bridge with distal flaring of the nose and prominent ears), fine and sparse hair, and malaligned teeth. Wallis and Beighton (1992) emphasized, possibly inappropriately, the hair and dental changes in entitling their report. INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Face \- Dysmorphic facial features Ears \- Prominent ears Eyes \- Blindness \- Microphthalmos \- Microcornea \- Sclerocornea Nose \- Narrow nasal bridge \- Distal nasal flaring Teeth \- Malaligned teeth SKIN, NAILS, & HAIR Hair \- Fine hair \- Sparse hair NEUROLOGIC Central Nervous System \- Mental retardation ▲ 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	RODRIGUES BLINDNESS	c1849332	3,980	omim	https://www.omim.org/entry/268320	2019-09-22T16:22:32	{"mesh": ["C535865"], "omim": ["268320"], "orphanet": ["1806"], "synonyms": ["Alternative titles", "MICROPHTHALMIA, MICROCORNEA, AND SCLEROCORNEA WITH SHORT STATURE AND HAIR AND DENTAL ABNORMALITIES"]}
Proventricular dilatation disease (PDD) is an incurable probably viral disease of psittacine birds. It was first recognized and described in 1978 by Dr. Hannis L. Stoddard. Since the first reported cases were involving species of macaw, the condition was termed macaw wasting syndrome.[1] ## Contents * 1 Clinical signs * 2 Cause * 3 Taxonomy * 4 Diagnosis * 5 References * 6 External links ## Clinical signs[edit] The clinical presentation of this disease varies with the individual as well as in severity of those symptoms. Often the symptoms include a gastrointestinal component, but many times birds suffering from this disease will present with neurologic signs as well, or in lieu of digestive anomalies. Gastrointestinal signs may include: Regurgitation, crop impaction, poor appetite, weight loss, or passage of undigested food in the feces.[2] Neurologic symptoms may include: Weakness, ataxia, paresis, proprioceptive deficits, head tremors, and rarely seizures.[2] Muscle wasting and a generalized poor body condition is usually found as well. The virus can also affect the Purkinje cells of the heart, the adrenal medulla, the brain, and the spinal cord. On necropsy the affected organs appear dilated and may include the crop, proventriculus, ventriculus, and small intestine. On histopathological examination the tissues will contain a lymphoplasmacytic infiltration in the peripheral and central nervous tissue. The causative virus is believed to commonly affect the myenteric plexuses which will also lead to the presentation of atrophied smooth muscle within the affected gastrointestinal organs.[2] It is this atrophy and loss of tone in the organs that causes the dilation and subsequent gastrointestinal symptoms which are commonly the first sign of disease for the owners. ## Cause[edit] In July 2008, a team of researchers at the University of California, San Francisco was able to identify a virus that may cause PDD, which they have named avian bornavirus (ABV).[3] A member of the Bornaviridae family, avian bornavirus was isolated in 71 percent of samples from infected birds, but in none of the healthy birds. The researchers were able to clone a full-length genome of the virus from avian tissue. Later analyses revealed that numerous distinct avian bornaviruses exist - not all of them cause PDD.[4] Gancz et al. succeeded in inducing PDD in cockatiels by inoculation of brain tissue from avian bornavirus-positive birds [5] while Gray et al. caused PDD in Patagonian conures by inoculation of a tissue-culture derived isolate of avian bornavirus.[6] Despite many reports, avian bornaviruses should not be stated as the cause of PDD.[citation needed] ## Taxonomy[edit] Family Bornaviridae: avian bornaviruses Genus Species Virus (Abbreviation) Orthobornavirus Passeriform 1 orthobornavirus canary bornavirus 1 (CnBV-1) canary bornavirus 2 (CnBV-2) canary bornavirus 3 (CnBV-3)) Passeriform 2 orthobornavirus estrildid finch bornavirus 1 (EsBV-1) Psittaciform 1 orthobornavirus parrot bornavirus 1 (PaBV-1) parrot bornavirus 2 (PaBV-2) parrot bornavirus 3 (PaBV-3) parrot bornavirus 4 (PaBV-4) parrot bornavirus 7 (PaBV-7) Psittaciform 2 orthobornavirus parrot bornavirus 5 (PaBV-5) Waterbird 1 orthobornavirus aquatic bird bornavirus 1 (ABBV-1) aquatic bird bornavirus 2 (ABBV-2) ## Diagnosis[edit] This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (May 2017) (Learn how and when to remove this template message) Traditional diagnosis included radiographs. The vet may ask for a follow up radiograph with a barium marker to collect more data on digestion to aid in confirmation of PDD. A tissue sample is a more reliable method as well but invasive yet the only definitive diagnosis with live parrots. The presence of avian bornaviruses may be detected in two ways: Testing fecal samples, cloacal swabs and blood for the presence of the virus or examining the bird's blood for ABV-specific antibodies by western blot or ELISA. All tests give a percentage of false positives and false negatives so detection of ABV or antibody against it does not mean that PDD will follow. The disease does not follow a clear path of development or transmission. ## References[edit] 1. ^ "All Creatures Health Care". 2. ^ a b c Harrison, and Lightfoot. 2006 Clinical Avian Medicine. Spix Publishing, Palm Beach, Florida. 3. ^ Kristen Bole (2008-07-29). "UCSF researchers identify virus behind mysterious parrot disease". UCSF News Office. Archived from the original on 2008-08-13. Retrieved 2008-07-31. 4. ^ Honkavuori, K.S., Shivaprasad, H.L., Williams, B.L., Quan, P.L., Hornig, M., Street, C., Palacios, G., Hutchison, S.K., Franca, M., Egholm, M., Briese, T. and Lipkin, W.I. (2008) Novel borna virus in psittacine birds with proventricular dilatation disease. Emerging infectious diseases 14(12), 1883-6.e 5. ^ Gancz, A.Y., Kistler, A.L., Greninger, A.L., Farnoushi, Y., Mechani, S., Perl, S., Berkowitz, A., Perez, N., Clubb, S., DeRisi, J.L., Ganem, D. and Lublin, A. (2009) Experimental induction of proventricular dilatation disease in cockatiels (Nymphicus hollandicus) inoculated with brain homogenates containing parrot bornavirus 4. Virology journal 6, 100.e 6. ^ Gray et al. Emerging Infectious Diseases, March 2010 ## External links[edit] * https://web.archive.org/web/20060616043500/http://www.stoppdd.org/problem/pdd_faq.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	Proventricular dilatation disease	None	3,981	wikipedia	https://en.wikipedia.org/wiki/Proventricular_dilatation_disease	2021-01-18T18:49:06	{"wikidata": ["Q3027962"]}
## Clinical Features Pinheiro et al. (1996) described a combination of precocious eruption and shedding of deciduous teeth, precocious eruption of secondary teeth with short rhomboid roots, and short, thin, slow growing nails in a 7-year-old boy born of consanguineous parents of Portuguese ancestry. Four other members of the same family (3 males, 1 female), also born of consanguineous parents, reportedly had the same complex of abnormalities. Five affected persons had 11 normal sibs, and 2 affected persons had 8 normal children. Pinheiro et al. (1996) suggested that this condition, which they designated odontomicronychial dysplasia, is a unique form of ectodermal dysplasia. Inheritance Pinheiro et al. (1996) concluded that odontomicronychial dysplasia is an autosomal recessive disorder. Nails \- Short, thin, slow growing nails Inheritance \- Autosomal recessive Teeth \- Precocious eruption and shedding of deciduous teeth \- Precocious eruption of secondary teeth \- Short rhomboid tooth roots ▲ 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	ODONTOMICRONYCHIAL DYSPLASIA	c1832473	3,982	omim	https://www.omim.org/entry/601319	2019-09-22T16:15:06	{"mesh": ["C537741"], "omim": ["601319"], "orphanet": ["1811"], "synonyms": ["Alternative titles", "ECTODERMAL DYSPLASIA, NAIL/TOOTH TYPE"]}
Cancer Kangri cancer SpecialtyDermatology/oncology Kangri cancer is a type of squamous-cell carcinoma of the skin. It is found only in Kashmir in the northwest of the Indian subcontinent. It occurs on the lower abdomen and inner thighs and is due to the use of a kanger, a ceramic pot covered with wicker-work, carried as a source of warmth during cold weather. One of the earliest records of the condition was made in 1881 by surgeons at the Kashmir Mission Hospital and its cause was recognized in the early 20th century by Arthur Neve.[1][2] Despite current knowledge of the cause of this condition, cases are still being reported.[3] Other conditions associated with prolonged use of kangri in this fashion include erythema ab igne, a reticulate hypermelanosis with erythema. ## Contents * 1 Signs and symptoms * 2 Risk factors * 3 Genetics * 4 Diagnosis * 5 Treatment * 5.1 Surgery * 5.2 Radiotherapy * 6 Prognosis * 7 Epidemiology * 8 See also * 9 References * 10 External links ## Signs and symptoms[edit] Most cases (80%) of squamous cell carcinoma attributed to ultraviolet radiation present in areas of the skin that are usually more exposed to sunlight (e.g., head, face, neck).[4] Although a particular form of squamous cell carcinoma, Kangri cancer is more often associated with the abdomen, thigh, and leg regions due to the usage and positioning of kangri pots, which come in close contact with these anatomical features.[5][6] Over time, the use of kangri pots to keep warm results in erythema ab igne, a precancerous keratotic growth that “take the shape of superficial, serpegenous, reticular blackish brown colored lesions.”[6] Eventually, the cells at the lesion site become more irregular in shape and form; the lesions ulcerate and may become itchy and bloody. The resulting irregular growth is the presentation of kangri cancer.[4][6] ## Risk factors[edit] Use of the kangri pot is the princple cause of kangri cancer. The pot holds hot wood and charcoal, and is put in direct contact with the skin of the abdomen and the thigh areas as a way to keep warm during winter in northern India.[6] Elements that are believed to contribute to the development of kangri cancer are heat, burning wood particles, smoke, soot, and tar of burnt chinar leaves.[7][8] In one study, researchers found that kangri cancer patients had a history of using a kangri for 5-6 hours a day, 3-4 months a year.[9] ## Genetics[edit] Beyond the behavioral risk factor of prolonged usage of kangri pots, researchers have begun to look at genetic mutations that may make some people more predisposed to develop kangri cancer. * In one study, people with kangri cancer were found to be approximately twice as likely as a control group to have a mutation in the TP53 gene (codon 72 polymorphism). Patients with higher grade tumors exhibited more proline amino acid mutations at this site.[10] * Another study confirmed the association of kangri Cancer and TP53, finding substitutions and insertions in 40% of the kangri cancer patients studied. The researchers observed a significant correlation with mutation status and age as well as with the presence of affected lymph nodes in patients. TP53 may, in the future, serve as “potential molecular marker and prognostic tool” for kangri cancer. Furthermore, PTEN mutations were found in two of thirty patients studied; though due to the small sample size, no useful conclusions could be postulated.[5] * Two polymorphisms of the HSP70 gene were discovered to be correlated with poor prognosis in cases of kangri cancer; the “Hsp70-2 A/G or G/G and Hsp70homC/C genotypes” could potentially be utilized to measure risk of kangri cancer development as well as to predict prognosis.[11] ## Diagnosis[edit] This section is empty. You can help by adding to it. (May 2018) ## Treatment[edit] ### Surgery[edit] In the treatment of kangri cancer, surgery is, most often, the first-line course of action to remove the primary tumor.[6] ### Radiotherapy[edit] External beam radiotherapy has been used in one person to prevent the relapse and growth of tumor metastases to the head and neck regions. The prophylactic applications of radiation have been noted as “encouraging” in this one case, reducing some tumors and eliminating others.[6] Another study with a couple of the same authors found that radiotherapy after surgery helped with the reduction and cure of head and neck tumors in additional cases. The researchers suggest that external beam radiotherapy should be part of the treatment course for patients who have or at risk of developing tumors in the head and neck areas.[4] ## Prognosis[edit] A research article from 1923 noted that the average life expectancy of those with kangri cancer was about fifteen months, though there have been records of people dying within one year and living for more than twenty years with kangri cancer.[7] Updated life expectancy is not found in more recent scientific publications. However, in 2013, it was noted that the progression from erythema ab igne to squamous cell carcinoma was between one and two decades.[9] It has been reported that about one-third to one-half of patients with kangri cancer show metastasis to local lymph nodes.[4] ## Epidemiology[edit] The first case of kangri cancer was reportedly recognized in 1819.[6] The incidence of kangri cancer is higher for those over age 50.[4][9] There is no definitive predominance of kangri cancer in either males or females. Some studies may point to higher prevalence in males while others observed higher prevalence in females.[4][9] In scientific literature, kangri cancer has only been attributed to the Kashmir region of northern India due to the traditional use of kangri pots. Kangri cancer is limited to this population, and thus, relatively little is known still, and there is much to be studied about the condition.[6][9][10] In 2017, a local Kashmir media outlet,The Kashmir Reader, reported that researchers and health care providers are optimistic about the reduced incidence of kangri cancer, citing the rise of thermal clothing and electric heating sources that are now used in place of kangri pots to keep warm.[12] ## See also[edit] * List of cutaneous conditions ## References[edit] 1. ^ Neve A (1900) Indian med. Gaz. 35, 81 2. ^ McCulloch HD (1910). "'Kangri cancer': A physiological aspect". Br Med J. 2 (2595): 912–913. doi:10.1136/bmj.2.2595.912-b. PMC 2336016. 3. ^ Wani I (2010). "Kangri cancer". Surgery. 147 (4): 586–588. doi:10.1016/j.surg.2009.10.025. 4. ^ a b c d e f Teli, Mohmad Ashraf; Khan, N. A.; Darzi, M. Ashraf; Gupta, Meenu; Tufail, A. (2009-01-01). "Recurrence pattern in squamous cell carcinoma of skin of lower extremities and abdominal wall (Kangri cancer) in Kashmir valley of Indian subcontinent: impact of various treatment modalities". Indian Journal of Dermatology. 54 (4): 342–346. doi:10.4103/0019-5154.57610. ISSN 1998-3611. PMC 2807710. PMID 20101335. 5. ^ a b Hussain, Ishraq; ul Rehman, Shakeel; Afroze, Dil; Zahoor, Lubna; Abdullah, Safiya; Hafiz, Adil; Shah, Zafar A.; Iqbal, Shabir; Shaffi, Mohammad (2009-05-31). "Mutational spectrum of conserved regions of TP53 and PTEN genes in Kangri cancer (of the skin) in the Kashmiri population". Mutation Research. 676 (1–2): 5–10. doi:10.1016/j.mrgentox.2009.02.011. ISSN 0027-5107. PMID 19486858. 6. ^ a b c d e f g h Teli, Ma; Darzi, Ma; Gupta, M.; Katoch, Ss (2008-07-01). "Recurrent Kangri cancer treated with external beam radiotherapy on a cobalt unit". Indian Journal of Cancer. 45 (3): 134–135. doi:10.4103/0019-509x.44074. ISSN 0019-509X. PMID 19018122. 7. ^ a b Neve, E. F. (1923-12-29). "Kangri-Burn Cancer". British Medical Journal. 2 (3287): 1255–1256. doi:10.1136/bmj.2.3287.1255. ISSN 0007-1447. PMC 2317796. PMID 20771404. 8. ^ Gothoskar, S. V.; Ranadive, K. J. (1966-12-01). "Experimental studies on the aetiology of "Kangri cancer"". British Journal of Cancer. 20 (4): 751–755. doi:10.1038/bjc.1966.86. ISSN 0007-0920. PMC 2008146. PMID 5964606. 9. ^ a b c d e Hassan, Iffat; Sajad, Peerzada; Reshi, Ruby (2013-05-01). "Histopathological analysis of the cutaneous changes due to kangri use in kashmiri population: a hospital based study". Indian Journal of Dermatology. 58 (3): 188–190. doi:10.4103/0019-5154.110825. ISSN 1998-3611. PMC 3667279. PMID 23723467. 10. ^ a b Pandith, Arshad A.; Khan, Nighat P.; Rashid, Nargis; Azad, Niyaz; Zaroo, Inam; Hafiz, Adil; Siddiqi, Mushtaq A. (2012-08-01). "Impact of codon 72 Arg > Pro single nucleotide polymorphism in TP53 gene in the risk of kangri cancer: a case control study in Kashmir". Tumor Biology. 33 (4): 927–933. doi:10.1007/s13277-012-0318-2. ISSN 1423-0380. PMID 22249977. 11. ^ Rehman, Shakeel Ul; Sameer, A. Syed; Zahoor, Lubna; Syeed, Nidda; Nanda, Mahoor S.; Hafiz, Adil; Shah, Zaffar A.; Siddiqi, Mushtaq A. (2009-05-01). "Polymorphic analysis of MHClinked Heat Shock Protein 70 genes: Their susceptibility and prognostic implication in Kangri cancer cases of Kashmiri population". Indian Journal of Human Genetics. 15 (2): 65–71. doi:10.4103/0971-6866.55218. ISSN 0971-6866. PMC 2910951. PMID 20680154. 12. ^ Correspondent, Reader (2017-02-05). "Specific to Kashmir, Kangri cancer on decline". Kashmir Reader. Retrieved 2017-04-21. ## External links[edit] * 'Kangri cancer' cases declining in Kashmir Valley (The Indian Express) * v * t * e Diseases of the skin and appendages by morphology Growths Epidermal * Wart * Callus * Seborrheic keratosis * Acrochordon * Molluscum contagiosum * Actinic keratosis * Squamous-cell carcinoma * Basal-cell carcinoma * Merkel-cell carcinoma * Nevus sebaceous * Trichoepithelioma Pigmented * Freckles * Lentigo * Melasma * Nevus * Melanoma Dermal and subcutaneous * Epidermal inclusion cyst * Hemangioma * Dermatofibroma (benign fibrous histiocytoma) * Keloid * Lipoma * Neurofibroma * Xanthoma * Kaposi's sarcoma * Infantile digital fibromatosis * Granular cell tumor * Leiomyoma * Lymphangioma circumscriptum * Myxoid cyst Rashes With epidermal involvement Eczematous * Contact dermatitis * Atopic dermatitis * Seborrheic dermatitis * Stasis dermatitis * Lichen simplex chronicus * Darier's disease * Glucagonoma syndrome * Langerhans cell histiocytosis * Lichen sclerosus * Pemphigus foliaceus * Wiskott–Aldrich syndrome * Zinc deficiency Scaling * Psoriasis * Tinea (Corporis * Cruris * Pedis * Manuum * Faciei) * Pityriasis rosea * Secondary syphilis * Mycosis fungoides * Systemic lupus erythematosus * Pityriasis rubra pilaris * Parapsoriasis * Ichthyosis Blistering * Herpes simplex * Herpes zoster * Varicella * Bullous impetigo * Acute contact dermatitis * Pemphigus vulgaris * Bullous pemphigoid * Dermatitis herpetiformis * Porphyria cutanea tarda * Epidermolysis bullosa simplex Papular * Scabies * Insect bite reactions * Lichen planus * Miliaria * Keratosis pilaris * Lichen spinulosus * Transient acantholytic dermatosis * Lichen nitidus * Pityriasis lichenoides et varioliformis acuta Pustular * Acne vulgaris * Acne rosacea * Folliculitis * Impetigo * Candidiasis * Gonococcemia * Dermatophyte * Coccidioidomycosis * Subcorneal pustular dermatosis Hypopigmented * Tinea versicolor * Vitiligo * Pityriasis alba * Postinflammatory hyperpigmentation * Tuberous sclerosis * Idiopathic guttate hypomelanosis * Leprosy * Hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized * Drug eruptions * Viral exanthems * Toxic erythema * Systemic lupus erythematosus Localized * Cellulitis * Abscess * Boil * Erythema nodosum * Carcinoid syndrome * Fixed drug eruption Specialized * Urticaria * Erythema (Multiforme * Migrans * Gyratum repens * Annulare centrifugum * Ab igne) Nonblanchable Purpura Macular * Thrombocytopenic purpura * Actinic/solar purpura Papular * Disseminated intravascular coagulation * Vasculitis Indurated * Scleroderma/morphea * Granuloma annulare * Lichen sclerosis et atrophicus * Necrobiosis lipoidica Miscellaneous disorders Ulcers * Hair * Telogen effluvium * Androgenic alopecia * Alopecia areata * Systemic lupus erythematosus * Tinea capitis * Loose anagen syndrome * Lichen planopilaris * Folliculitis decalvans * Acne keloidalis nuchae Nail * Onychomycosis * Psoriasis * Paronychia * Ingrown nail Mucous membrane * Aphthous stomatitis * Oral candidiasis * Lichen planus * Leukoplakia * Pemphigus vulgaris * Mucous membrane pemphigoid * Cicatricial pemphigoid * Herpesvirus * Coxsackievirus * Syphilis * Systemic histoplasmosis * Squamous-cell carcinoma * v * t * e Radiation-related disorders / Photodermatoses Ultraviolet/ionizing * Sunburn * Phytophotodermatitis * Solar urticaria * Polymorphous light eruption * Benign summer light eruption * Juvenile spring eruption * Acne aestivalis * Hydroa vacciniforme * Solar erythema Non-ionizing Actinic rays * Actinic keratosis * Atrophic actinic keratosis * Hyperkeratotic actinic keratosis * Lichenoid actinic keratosis * Pigmented actinic keratosis * Actinic cheilitis * Actinic granuloma * Actinic prurigo * Chronic actinic dermatitis Infrared/heat * Erythema ab igne (Kangri ulcer * Kairo cancer * Kang cancer * Peat fire cancer) * Cutis rhomboidalis nuchae * Poikiloderma of Civatte Other * Radiation dermatitis * Acute * Chronic radiodermatitis) * Favre–Racouchot syndrome * Photoaging * Photosensitivity with HIV infection * Phototoxic tar dermatitis [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Kangri cancer	None	3,983	wikipedia	https://en.wikipedia.org/wiki/Kangri_cancer	2021-01-18T18:39:06	{"wikidata": ["Q6362874"]}
Hereditary antithrombin deficiency is a disorder of blood clotting. People with this condition are at higher than average risk for developing abnormal blood clots, particularly a type of clot that occurs in the deep veins of the legs. This type of clot is called a deep vein thrombosis (DVT). Affected individuals also have an increased risk of developing a pulmonary embolism (PE), which is a clot that travels through the bloodstream and lodges in the lungs. In hereditary antithrombin deficiency, abnormal blood clots usually form only in veins, although they may rarely occur in arteries. About half of people with hereditary antithrombin deficiency will develop at least one abnormal blood clot during their lifetime. These clots usually develop after adolescence. Other factors can increase the risk of abnormal blood clots in people with hereditary antithrombin deficiency. These factors include increasing age, surgery, or immobility. The combination of hereditary antithrombin deficiency and other inherited disorders of blood clotting can also influence risk. Women with hereditary antithrombin deficiency are at increased risk of developing an abnormal blood clot during pregnancy or soon after delivery. They also may have an increased risk for pregnancy loss (miscarriage) or stillbirth. ## Frequency Hereditary antithrombin deficiency is estimated to occur in about 1 in 2,000 to 3,000 individuals. Of people who have experienced an abnormal blood clot, about 1 in 20 to 200 have hereditary antithrombin deficiency. ## Causes Hereditary antithrombin deficiency is caused by mutations in the SERPINC1 gene. This gene provides instructions for producing a protein called antithrombin (previously known as antithrombin III). This protein is found in the bloodstream and is important for controlling blood clotting. Antithrombin blocks the activity of proteins that promote blood clotting, especially a protein called thrombin. Most of the mutations that cause hereditary antithrombin deficiency change single protein building blocks (amino acids) in antithrombin, which disrupts its ability to control blood clotting. Individuals with this condition do not have enough functional antithrombin to inactivate clotting proteins, which results in the increased risk of developing abnormal blood clots. ### Learn more about the gene associated with Hereditary antithrombin deficiency * SERPINC1 ## Inheritance Pattern Hereditary antithrombin deficiency is typically inherited in an autosomal dominant pattern, which means one altered copy of the SERPINC1 gene in each cell is sufficient to cause the disorder. Inheriting two altered copies of this gene in each cell is usually incompatible with life; however, a few severely affected individuals have been reported with mutations in both copies of the SERPINC1 gene in each cell. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: 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 antithrombin deficiency	c0272375	3,984	medlineplus	https://medlineplus.gov/genetics/condition/hereditary-antithrombin-deficiency/	2021-01-27T08:25:10	{"gard": ["6148"], "mesh": ["D020152"], "omim": ["107300"], "synonyms": []}
## Clinical Features In 2 sibships of a highly consanguineous Mexican kindred, Barros-Nunes and Rivas (1993) identified 3 males with hydrocephalus and 3 males with microcephaly. The 20-month-old proband was diagnosed by computed tomography with hydrocephalus due to aqueductal stenosis. He had acrocephaly, cranial hypertensive symptoms, and generalized convulsive seizures resistant to treatment. He was not able to crawl, stand up unsupported, or control his head. Physical examination showed hyporeactivity, photomotor hyporeflexia, generalized muscular hypertonia and hyperreflexia, positive Babinski sign, convergent strabismus, hypertelorism, highly arched palate, retrognathia, short neck, normal thorax, prominent abdomen without visceromegaly, bilateral cryptorchidism, small penis, and small hands with adducted thumbs. The authors suggested that a different recessive gene might be responsible for the microcephaly. Haverkamp et al. (1999) studied a series of 35 patients with congenital internal hydrocephalus and aqueductal stenosis. The patients included a brother and sister with a normal phenotype except for the aqueductal stenosis. The parents were consanguineous. Hamada et al. (1999) described a Japanese brother and sister who presented in fetal life with isolated hydrocephalus due to aqueductal stenosis. Inheritance Barros-Nunes and Rivas (1993) suggested that hydrocephalus due to congenital stenosis of the aqueduct of Sylvius in the Mexican kindred they reported was inherited in an autosomal recessive manner. They cited the family reported by Petrus et al. (1981) and the family reported by Vanlieferinghen et al. (1987) as other examples of autosomal recessive inheritance of aqueductal stenosis. Haverkamp et al. (1999) and Hamada et al. (1999) suggested autosomal recessive inheritance of hydrocephalus due to aqueductal stenosis in the families they 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	HYDROCEPHALUS DUE TO CONGENITAL STENOSIS OF AQUEDUCT OF SYLVIUS	c0265216	3,985	omim	https://www.omim.org/entry/236635	2019-09-22T16:26:58	{"doid": ["10908"], "mesh": ["C536078"], "omim": ["236635"], "synonyms": ["Alternative titles", "AQUEDUCTAL STENOSIS"]}
Cornelia de Lange syndrome Other namesBushy syndrome One-year-old boy with Cornelia de Lange syndrome SpecialtyMedical genetics Cornelia de Lange syndrome (CdLS) is a genetic disorder. People with this syndrome experience a range of physical, cognitive, and medical challenges ranging from mild to severe. The syndrome has a widely varied phenotype, meaning people with the syndrome have varied features and challenges. The typical features of CdLS include thick or long eyebrows, a small nose, small stature, developmental delay, long or smooth philtrum, thin upper lip and downturned mouth.[1] The syndrome is named after Dutch pediatrician Cornelia Catharina de Lange, who described it in 1933. It is often termed Brachmann de Lange syndrome or Bushy syndrome and is also known as Amsterdam dwarfism. Its exact incidence is unknown, but it is estimated at 1 in 10,000 to 30,000. ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 4 Treatment * 5 History * 6 References * 7 External links ## Signs and symptoms[edit] This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (September 2016) (Learn how and when to remove this template message) The phenotype of CdLS is highly varied and is described as a spectrum; from Classic CdLS (with a greater number of key features) to mild variations with only a few features. Some people will have a small number of features but don't have CdLS.[1] Key features: * Long and/or thick eyebrows * Short nose * Concave nasal ridge and/or upturned nasal tip * Long and/or smooth philtrum * Thin upper lip vermilion and/or downturned corners of mouth * Missing fingers or toes * Congenital diaphragmatic hernia Other suggestive features: * Developmental delay and/or intellectual disability * Small prenatal and birth size / weight * Small stature * Microcephaly (prenatally and/or postnatally) * Small hands and/or feet * Short fifth finger * Hirsutism The following health conditions are more common in people with CdLS than in the general population. * Respiratory illness * Heart defects (e.g., pulmonary stenosis, VSD, ASD, coarctation of the aorta) * Hearing impairment * Vision abnormalities (e.g., ptosis, nystagmus, high myopia, hypertropia) * Partial joining of the second and third toes * Incurved 5th fingers (clinodactyly) * Gastroesophageal reflux * Gastrointestinal abnormalities * Musculoskeletal problems * Scoliosis * Social anxiety * Seizures * Cleft palate * Feeding problems Children with this syndrome are often found to have long eyelashes, bushy eyebrows and synophrys (joined eyebrows). Body hair can be excessive and affected individuals are often shorter than their immediate family members. They present a characteristic facial phenotype.[2] Children with CdLS often suffer from gastrointestinal tract difficulties, particularly gastroesophageal reflux. Vomiting, intermittent poor appetite, constipation, diarrhea or gaseous distention are known to be a regularity in cases where the GI tract problems are acute. Symptoms may range from mild to severe. People with CdLS may exhibit behaviours that have been described as "autistic-like," including self-stimulation, aggression, self-injury or strong preference to a structured routine. Behavior problems in CdLS are not inevitable. Many behaviour issues associated with CdLS are reactive (i.e., something happens within the person's body or environment to bring on the behavior) and cyclical (comes and goes). Often, an underlying medical issue, pain, social anxiety, environmental or caregiver stress can be associated with a change behaviour. If pain or a medical issue is the cause, once treated, the behaviour diminishes. There is evidence for some features of premature aging including the early development of Barrett’s esophagus, osteoporosis present in the teenage years, premature greying of hair and some changes to the skin of the face causing a more aged appearance compared to chronological age.[3] ## Causes[edit] The vast majority of cases are thought to be due to spontaneous genetic mutations.[1] It can be associated with mutations affecting the cohesin complex.[4] As of 2018, it was confirmed that 500 genetic mutations have been associated with the condition; occurring on 7 different genes. In around 30% of cases of CdLS the genetic cause remains undiscovered. The wide variation in phenotype is attributed to a high degree of somatic mosaicism in CdLS as well as the different genes and type of mutations. For this reason people with CdLS can have very different appearance, abilities, and associated health issues.[5] Name OMIM Gene Appx. % Notes CDLS1 122470 NIPBL 50% A gene responsible for CdLS on chromosome 5 was discovered in 2004 jointly by researchers at the Children's Hospital of Philadelphia, USA[6] and researchers at Newcastle University, UK.[7] CDLS2 300590 SMC1A 5% In 2006, a second gene, on the X chromosome, was found by Italian scientists. CDLS3 610759 SMC3 1% A third gene discovery was announced in 2007. The gene is on chromosome 10 and was also discovered by the research team in Philadelphia. The latter two genes seem to correlate with a milder form of the syndrome. In 2004, researchers at the Children's Hospital of Philadelphia (United States) and the University of Newcastle upon Tyne (England) identified a gene (NIPBL) on chromosome 5 that causes CdLS when it is mutated. Since then, additional genes have been found (SMC1A, SMC3 and HDAC8, RAD21) that cause CdLS when changed. In July 2012, the fourth "CdLS gene"—HDAC8—was announced. HDAC8 is an X-linked gene, meaning it is located on the X chromosome. Individuals with CdLS who have the gene change in HDAC8 make up just a small portion of all people with CdLS.[8] Evidence of a linkage at chromosome 3q26.3 is mixed.[9] Genetic alterations associated with CdLS have been identified in genes NIPBL, SMC1A and SMC3 as well as the more recently identified genes RAD21 and HDAC8.[10] All of these genetic alterations occurring in CdLS patients affect proteins that function in the cohesin pathway.[10] SMC1A, SMC3 and RAD21 proteins are structural components of the cohesin ring complex. NIPBL is involved in the loading of the cohesin ring onto chromosomes, and HDAC8 deacylates SMC3 to facilitate its function. The cohesin pathway is involved in cohesion of sister chromatids during mitosis, DNA repair, chromosome segregation and the regulation of developmental gene expression. Defects in these functions are theorised to underlie some of the features of CdLS.[11] In particular, defective DNA repair may underlie the features of premature aging.[3] ## Diagnosis[edit] The diagnosis of CdLS is primarily based on clinical findings by a clinical geneticist; and in some cases may be confirmed through laboratory testing.[5] ## Treatment[edit] Often, an interdisciplinary approach is recommended to treat the issues associated with CdLS. A team for promoting the child's well-being often includes speech, occupational and physical therapists, teachers, physicians, and parents.[12] In August 2020 Briton Major Chris Brannigan walked the length of Britain barefoot to raise half a million pounds, which is being used to engineer the first gene-targeted therapy for Cornelia de Lange Syndrome. If successful this will be the first treatment for CdlS. [13] ## History[edit] The first documented case was in 1916 by Winfried Robert Clemens Brachmann (1888–1969), a German physician who wrote about the distinct features of the disease from his 19-year-old patient,[14] followed in 1933 by Cornelia Catharina de Lange (1871–1950),[15] a Dutch pediatrician after whom the disorder has been named.[16] CdLS was formerly known as Brachmann-de Lange Syndrome.[17] ## References[edit] 1. ^ a b c Hennekam, Raoul C.; Balkom, Ingrid D. C. Van; Tümer, Zeynep; Shi, Angell; Rigamonti, Claudia; Richman, David; Redeker, Egbert; Quaglio, Ana L.; Potter, Carol J. (October 2018). "Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement" (PDF). Nature Reviews Genetics. 19 (10): 649–666. doi:10.1038/s41576-018-0031-0. ISSN 1471-0064. PMID 29995837. 2. ^ Basel-Vanagaite, L.; Wolf, L.; Orin, M.; Larizza, L.; Gervasini, C.; Krantz, I.D.; Deardoff, M.A. (2016). "Recognition of the Cornelia de Lange syndrome phenotype with facial dysmorphology novel analysis". Clinical Genetics. 89 (5): 557–563. doi:10.1111/cge.12716. PMID 26663098. 3. ^ a b Kline AD, Grados M, Sponseller P, Levy HP, Blagowidow N, Schoedel C, Rampolla J, Clemens DK, Krantz I, Kimball A, Pichard C, Tuchman D (2007). "Natural history of aging in Cornelia de Lange syndrome". Am J Med Genet C Semin Med Genet. 145C (3): 248–60. doi:10.1002/ajmg.c.30137. PMC 4902018. PMID 17640042. 4. ^ Liu J, Krantz ID (October 2009). "Bushy Syndrome, cohesin, and beyond". Clin. Genet. 76 (4): 303–14. doi:10.1111/j.1399-0004.2009.01271.x. ISSN 0009-9163. PMC 2853897. PMID 19793304. 5. ^ a b Kline, Antonie D.; Moss, Joanna F.; Selicorni, Angelo; Bisgaard, Anne-Marie; Deardorff, Matthew A.; Gillett, Peter M.; Ishman, Stacey L.; Kerr, Lynne M.; Levin, Alex V. (2018-07-11). "Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement" (PDF). Nature Reviews Genetics. 19 (10): 649–666. doi:10.1038/s41576-018-0031-0. ISSN 1471-0056. PMID 29995837. 6. ^ Krantz ID, McCallum J, DeScipio C, et al. (2004). "Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B". Nature Genetics. 36 (6): 631–5. doi:10.1038/ng1364. PMC 4902017. PMID 15146186. 7. ^ Tonkin E, Wang TJ, Lisgo S, Bamshad MJ, Strachan T (2004). "NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome". Nature Genetics. 36 (6): 636–641. doi:10.1038/ng1363. PMID 15146185. 8. ^ "HDAC8 FAQ Sheet" (PDF). CdLS Foundation Web site. Cornelia de Lange Syndrome Foundation. Archived from the original (PDF) on 3 September 2013. Retrieved 12 February 2013. 9. ^ Krantz ID, Tonkin E, Smith M, et al. (June 2001). "Exclusion of linkage to the CDL1 gene region on chromosome 3q26.3 in some familial cases of Cornelia de Lange syndrome". American Journal of Medical Genetics. 101 (2): 120–9. doi:10.1002/1096-8628(20010615)101:2<120::AID-AJMG1319>3.0.CO;2-G. PMC 4896160. PMID 11391654. 10. ^ a b Boyle MI, Jespersgaard C, Brøndum-Nielsen K, Bisgaard AM, Tümer Z (2015). "Cornelia de Lange syndrome". Clin. Genet. 88 (1): 1–12. doi:10.1111/cge.12499. PMID 25209348. 11. ^ Pié J, Gil-Rodríguez MC, Ciero M, López-Viñas E, Ribate MP, Arnedo M, Deardorff MA, Puisac B, Legarreta J, de Karam JC, Rubio E, Bueno I, Baldellou A, Calvo MT, Casals N, Olivares JL, Losada A, Hegardt FG, Krantz ID, Gómez-Puertas P, Ramos FJ (2010). "Mutations and variants in the cohesion factor genes NIPBL, SMC1A, and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome". Am. J. Med. Genet. A. 152A (4): 924–9. doi:10.1002/ajmg.a.33348. PMC 2923429. PMID 20358602. 12. ^ "CdLS Foundation – Treatment Protocols". 12 February 2013. Retrieved 12 February 2013. 13. ^ https://www.bbc.com/news/amp/uk-england-wiltshire-53757274... 14. ^ Brachmann W (1916). "Ein Fall von symmetrischer Monodaktylie durch Ulnadefekt, mit symmetrischer Flughautbildung in den Ellenbeugen, sowie anderen Abnormitaeten (Zwerghaftigkeit, Halsrippen, Behaarung) (A case of symmetrical monodactyly, representing ulnar deficiency, with symmetrical antecubital webbing and other abnormalities, (dwarfism, cervical ribs, hirsutism))". Jahrbuch für Kinderheilkunde und physische Erziehung. 84: 225–235. 15. ^ de Lange C (1933). "Sur un type nouveau de degenerescence (typus Amstelodamensis)". Arch. Med. Enfants. 36: 713–719. 16. ^ "Brachmann-de Lange syndrome". 17. ^ Aitken, Kenneth J. (2009). A-Z of Genetic Factors in Autism: A Handbook for Professionals. London: Jessica Kingsley. pp. 172–173. ISBN 9781843109761. Retrieved December 10, 2015. ## External links[edit] Classification D * ICD-10: Q87.1 (ILDS Q87.170) * ICD-9-CM: 759.89 * OMIM: 122470 * MeSH: D003635 * DiseasesDB: 29651 External resources * eMedicine: ped/482 Wikimedia Commons has media related to Cornelia de Lange syndrome. * GeneReviews/NCBI/UW/NIH entry on Cornelia de Lange syndrome * v * t * e Nucleus diseases Telomere * Revesz syndrome Nucleolus * Treacher Collins syndrome * Spinocerebellar ataxia 7 * Cajal body: Spinal muscular atrophy Centromere * CENPJ * Seckel syndrome 4 Other * AAAS * Triple-A syndrome * Laminopathy * SMC1A/SMC3 * Cornelia de Lange Syndrome * SETBP1 * Schinzel–Giedion syndrome see also nucleus [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Cornelia de Lange syndrome	c0270972	3,986	wikipedia	https://en.wikipedia.org/wiki/Cornelia_de_Lange_syndrome	2021-01-18T18:32:25	{"gard": ["10109"], "mesh": ["D003635"], "umls": ["C0270972"], "icd-9": ["759.89"], "orphanet": ["199"], "wikidata": ["Q1133289"]}
A number sign (#) is used with this entry because Culler-Jones syndrome (CJS) is caused by heterozygous mutation in the GLI2 gene (165230) on chromosome 2q14. Mutation in the GLI2 gene also causes holoprosencephaly-9 (HPE9; 610829), or HPE-like features, which may be considered at the severe end of the spectrum of features associated with GLI2 mutations. Description Culler-Jones syndrome (CJS) is an autosomal dominant disorder characterized by hypopituitarism, mainly growth hormone deficiency, and/or postaxial polydactyly. The phenotype is highly variable, and some patients may have midline facial defects and developmental delay. The disorder shows incomplete penetrance and variable expressivity (summary by Franca et al., 2010). Clinical Features Culler and Jones (1984) reported a boy (patient 2) with hypopituitarism and bilateral postaxial polydactyly. He had bilateral cryptorchidism and microphallus. Brain imaging showed an empty sella. His father and older brother had postaxial polydactyly, but no hormone deficiencies. In a follow-up of the family reported by Culler and Jones (1984), Roessler et al. (2005) noted that the proband's older brother with postaxial polydactyly had a son with panhypopituitarism and bilateral postaxial polydactyly. Brain MRI showed aplasia of the pituitary. His endocrine problems responded well to hormone replacement. Franca et al. (2010) reported a large 4-generation Brazilian family with variable manifestations of polydactyly and pituitary anomalies. The proband was a 7-year-old girl who presented with growth failure and severely delayed psychomotor development associated with early-onset seizures. Endocrine work-up showed severe pituitary hormone deficiencies resulting in short stature (-5.4 SD), delayed bone age, hypogonadotropic hypogonadism, and low thyroid-stimulating hormone. Brain MRI showed a hypoplastic anterior pituitary, an ectopic posterior pituitary, and diminished brain size with asymmetry of the cerebral hemispheres, but no HPE-like abnormalities. She also had a high-pitched voice and bilateral postaxial polydactyly. There were no midline facial defects. Family screening identified 8 maternal relatives with postaxial polydactyly, 3 of whom had growth hormone deficiency associated with anterior pituitary hypoplasia and an ectopic posterior pituitary. One of the relatives with growth hormone deficiency had deficiency of several pituitary hormones. Two additional smaller families were also reported. A 12-year-old boy was born with cleft lip and palate, flat nasal bridge, and cryptorchidism. He later was found to have short stature due to growth hormone deficiency and partial ACTH deficiency. Brain imaging showed a hypoplastic anterior pituitary and an ectopic posterior pituitary lobe; there were no signs of HPE. The proband of the third family had severe developmental delay with seizures, hypopituitarism of multiple hormones associated with a hypoplastic anterior pituitary, and ADH deficiency with diabetes insipidus associated with lack of a posterior pituitary on brain imaging. In the latter 2 cases, the parents transmitting the mutations were clinically unaffected. Franca et al. (2013) screened 41 Brazilian patients with isolated growth hormone deficiency and 136 Brazilian patients with combined pituitary hormone deficiency (CPHD) for variants in the GLI2 gene. Eighteen different heterozygous variants were identified in 24 patients, including 1 with isolated GH deficiency and 23 with CPHD. Two patients also had diabetes insipidus, indicating deficiencies of both the anterior and posterior pituitary lobes. Brain imaging showed an ectopic posterior pituitary lobe in 16 patients and an undetectable posterior lobe in 4. None of the patients had signs of HPE, midline facial defects, or polydactyly. Functional studies of the identified GLI2 variants were not performed. Franca et al. (2013) concluded that patients with CPHD and an ectopic posterior pituitary lobe, with or without polydactyly or midline facial defects, are candidates for GLI2 study. Bear et al. (2014) screened a large cohort of approximately 400 individuals with HPE spectrum disorders, including those with pituitary deficiencies, for variations in the GLI2 gene, and combined these data with patients with GLI2 variants collected from the published literature. Variants were identified in 112 individuals from 65 kindreds, including 30 individuals (27%) who had not previously been reported. Forty-three individuals had truncating mutations, whereas the rest had missense variants of unknown significance; functional studies of the variants were not performed. Only 1 of the 43 patients with truncating mutations had frank HPE (this patient was previously reported by Bertolacini et al., 2012). Most (67%) of the 112 patients with GLI2 variants studied by Bear et al. (2014) were described as having normal facial features or were nondysmorphic. Individuals with truncating mutations were more likely to have pituitary anomalies and/or polydactyly compared to those with variants of unknown significance. Those with truncating mutations also tended to have a common facial phenotype, with midface hypoplasia, cleft lip/palate, and hypotelorism. Bear et al. (2014) concluded that there is a well-defined phenotype in individuals with pathogenic GLI2 mutations, which does not typically include HPE. Rather, the phenotype includes anterior pituitary anomalies and postaxial polydactyly, although not all individuals with predicted pathogenic mutations have both findings. Inheritance The transmission pattern of Culler-Jones syndrome in the family reported by Culler and Jones (1984) and Roessler et al. (2005) was consistent with autosomal dominant inheritance and incomplete penetrance. The transmission pattern of CJS in the families reported by Franca et al. (2010) was consistent with autosomal dominant inheritance with incomplete penetrance and variable expressivity. Molecular Genetics In affected members of a 3-generation family with variable manifestations of CJS, originally reported by Culler and Jones (1984), Roessler et al. (2005) identified a heterozygous truncating mutation in the GLI2 gene (165230.0008). In affected members of 3 unrelated families with variable manifestations of hypopituitarism and postaxial polydactyly without signs of HPE, Franca et al. (2010) identified 3 different heterozygous frameshift or truncating mutations in the GLI2 gene (see, e.g., 165230.0008 and 165230.0009). Franca et al. (2010) suggested that the incomplete penetrance and highly variable expressivity observed in this phenotype result from a complex pattern of inheritance combining multiple environmental and genetic factors, such as variants at other loci or digenic inheritance. INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Face \- Midface hypoplasia (in some patients) Eyes \- Hypotelorism (in some patients) Mouth \- Cleft lip (in some patients) \- Cleft palate (in some patients) GENITOURINARY External Genitalia (Male) \- Micropenis \- Cryptorchidism SKELETAL Hands \- Postaxial polydactyly (in some patients) Feet \- Postaxial polydactyly (in some patients) NEUROLOGIC Central Nervous System \- Delayed psychomotor development (in some patients) \- Anterior pituitary hypoplasia \- Ectopic posterior pituitary \- Thin pituitary stalk ENDOCRINE FEATURES \- Hypopituitarism \- Combined pituitary hormone deficiency \- Low or absent growth hormone \- Low or absent thyroid-stimulating hormone \- Low or absent prolactin \- Hypogonadotropic hypogonadism \- Low ACTH \- Low ADH (in some patients) \- Diabetes insipidus (in some patients) MISCELLANEOUS \- Variable phenotype \- Incomplete penetrance \- Variable expressivity MOLECULAR BASIS \- Caused by mutation in the GLI-kruppel family member 2 gene (GLI2, 165230.0008 ) ▲ 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	CULLER-JONES SYNDROME	c4014479	3,987	omim	https://www.omim.org/entry/615849	2019-09-22T15:50:50	{"doid": ["0080328"], "omim": ["615849"], "orphanet": ["420584"], "synonyms": ["Alternative titles", "Culler-Jones syndrome", "PALLISTER-HALL SYNDROME 2, FORMERLY"]}
Positional alcohol nystagmus (PAN) is nystagmus (visible jerkiness in eye movement) produced when the head is placed in a sideways position. PAN occurs when the specific gravity of the membrane space of the semicircular canals in the ear differs from the specific gravity of the fluid in the canals because of the presence of alcohol. ## Contents * 1 PAN I * 2 PAN II * 3 Relationship between PAN and the effects of intoxication * 4 PAN versus testing for HGN in intoxicated individuals * 5 See also * 6 References ## PAN I[edit] When a person consumes alcohol, the alcohol is carried by the bloodstream and diffused into the water compartments of the body. Normally, the specific gravity of a canal membrane is the same as the specific gravity of the surrounding fluid. Because of this, even though the Earth's gravity is a constant force of acceleration, the semicircular canals do not respond to it. Alcohol has a lighter specific gravity than water. When alcohol enters the canal membrane via capillaries, the specific gravity of the membrane is lower than that of the surrounding fluid. The alcohol does diffuse from the membrane to the fluid, but it does so very slowly. While the specific gravity of the membrane is lower than the specific gravity of the extracellular fluid, the hair cells on the membrane become responsive to the Earth's gravity.[1] This is the condition of PAN I. PAN I is characterized by a nystagmus to the right when the right side of the head is down. It is typically present during a rising and peak Blood Alcohol Concentration (BAC). ## PAN II[edit] As soon as a person starts drinking, the body begins to process and eliminate the alcohol. The rate of elimination is fairly constant. Initially, the rate of absorption exceeds the rate of elimination, which results in a rising BAC. Some time after a person stops drinking, the rate of absorption drops below the rate of elimination, and the BAC begins falling. As alcohol is eliminated from the body, it is removed from the membrane of the semicircular canal faster than the surrounding fluid. This creates the reverse situation of PAN I, as the specific gravity of the fluid is now lower than that of the membrane. This results in PAN II. PAN II is characterized by a nystagmus to the right when the left side of the head is down. ## Relationship between PAN and the effects of intoxication[edit] The overstimulation of the semicircular canals during PAN I and PAN II is associated with the unsteadiness, nausea, and vertigo felt by intoxicated people. PAN I is more associated with postural problems (e.g. standing and walking) while PAN II has been more associated with the feelings of a hangover.[2] There is a brief period between PAN I and PAN II when the alcohol concentrations in the canal membrane and extracellular fluid are in equilibrium. During this time, neither PAN I nor PAN II is present. ## PAN versus testing for HGN in intoxicated individuals[edit] Horizontal Gaze Nystagmus (HGN) testing is a common practice used by law enforcement in the United States in the identification of persons who are intoxicated or under the influence of a controlled substance. The key difference between recognizing PAN and horizontal gaze nystagmus is the position of the subject's head in relation to the body. PAN is identified when the head is tilted to one side or the other. In order for HGN to be properly identified, the head must be positioned in line with the spine. Because of this, if the head is tilted towards the side when an evaluation for HGN is given, PAN may be induced and give a "false positive" for HGN. Some defendants may claim or argue that the nystagmus observed by an officer was positional and not horizontal gaze.[3] ## See also[edit] * Optokinetic reflex * Nystagmus ## References[edit] 1. ^ Karch, Steven B. (2007). Forensic Issues in Alcohol Testing. Boca Raton: CRC Press. ISBN 978-1-4200-5445-3. 2. ^ Fregly AR, Bergstedt M, Graybiel A (1968). "Relationships between blood alcohol, positional alcohol nystagmus and postural equilibrium". Q J Stud Alcohol. 28 (1): 11–21. PMID 5339889. 3. ^ Advanced DUI Investigation: A Training and Reference Manual, Daniel J. Haggin, Charles C Thomas (Publisher), 2005, pg. 144. * K. E. Money; W. S. Myles (8 February 1974). "Heavy water nystagmus and effects of alcohol". Nature. 247: 404–405. * v * t * e * Diseases of the human eye Adnexa Eyelid Inflammation * Stye * Chalazion * Blepharitis * Entropion * Ectropion * Lagophthalmos * Blepharochalasis * Ptosis * Blepharophimosis * Xanthelasma * Ankyloblepharon Eyelash * Trichiasis * Madarosis Lacrimal apparatus * Dacryoadenitis * Epiphora * Dacryocystitis * Xerophthalmia Orbit * Exophthalmos * Enophthalmos * Orbital cellulitis * Orbital lymphoma * Periorbital cellulitis Conjunctiva * Conjunctivitis * allergic * Pterygium * Pseudopterygium * Pinguecula * Subconjunctival hemorrhage Globe Fibrous tunic Sclera * Scleritis * Episcleritis Cornea * Keratitis * herpetic * acanthamoebic * fungal * Exposure * Photokeratitis * Corneal ulcer * Thygeson's superficial punctate keratopathy * Corneal dystrophy * Fuchs' * Meesmann * Corneal ectasia * Keratoconus * Pellucid marginal degeneration * Keratoglobus * Terrien's marginal degeneration * Post-LASIK ectasia * Keratoconjunctivitis * sicca * Corneal opacity * Corneal neovascularization * Kayser–Fleischer ring * Haab's striae * Arcus senilis * Band keratopathy Vascular tunic * Iris * Ciliary body * Uveitis * Intermediate uveitis * Hyphema * Rubeosis iridis * Persistent pupillary membrane * Iridodialysis * Synechia Choroid * Choroideremia * Choroiditis * Chorioretinitis Lens * Cataract * Congenital cataract * Childhood cataract * Aphakia * Ectopia lentis Retina * Retinitis * Chorioretinitis * Cytomegalovirus retinitis * Retinal detachment * Retinoschisis * Ocular ischemic syndrome / Central retinal vein occlusion * Central retinal artery occlusion * Branch retinal artery occlusion * Retinopathy * diabetic * hypertensive * Purtscher's * of prematurity * Bietti's crystalline dystrophy * Coats' disease * Sickle cell * Macular degeneration * Retinitis pigmentosa * Retinal haemorrhage * Central serous retinopathy * Macular edema * Epiretinal membrane (Macular pucker) * Vitelliform macular dystrophy * Leber's congenital amaurosis * Birdshot chorioretinopathy Other * Glaucoma / Ocular hypertension / Primary juvenile glaucoma * Floater * Leber's hereditary optic neuropathy * Red eye * Globe rupture * Keratomycosis * Phthisis bulbi * Persistent fetal vasculature / Persistent hyperplastic primary vitreous * Persistent tunica vasculosa lentis * Familial exudative vitreoretinopathy Pathways Optic nerve Optic disc * Optic neuritis * optic papillitis * Papilledema * Foster Kennedy syndrome * Optic atrophy * Optic disc drusen Optic neuropathy * Ischemic * anterior (AION) * posterior (PION) * Kjer's * Leber's hereditary * Toxic and nutritional Strabismus Extraocular muscles Binocular vision Accommodation Paralytic strabismus * Ophthalmoparesis * Chronic progressive external ophthalmoplegia * Kearns–Sayre syndrome palsies * Oculomotor (III) * Fourth-nerve (IV) * Sixth-nerve (VI) Other strabismus * Esotropia / Exotropia * Hypertropia * Heterophoria * Esophoria * Exophoria * Cyclotropia * Brown's syndrome * Duane syndrome Other binocular * Conjugate gaze palsy * Convergence insufficiency * Internuclear ophthalmoplegia * One and a half syndrome Refraction * Refractive error * Hyperopia * Myopia * Astigmatism * Anisometropia / Aniseikonia * Presbyopia Vision disorders Blindness * Amblyopia * Leber's congenital amaurosis * Diplopia * Scotoma * Color blindness * Achromatopsia * Dichromacy * Monochromacy * Nyctalopia * Oguchi disease * Blindness / Vision loss / Visual impairment Anopsia * Hemianopsia * binasal * bitemporal * homonymous * Quadrantanopia subjective * Asthenopia * Hemeralopia * Photophobia * Scintillating scotoma Pupil * Anisocoria * Argyll Robertson pupil * Marcus Gunn pupil * Adie syndrome * Miosis * Mydriasis * Cycloplegia * Parinaud's syndrome Other * Nystagmus * Childhood blindness Infections * Trachoma * Onchocerciasis * v * t * e 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	Positional alcohol nystagmus	None	3,988	wikipedia	https://en.wikipedia.org/wiki/Positional_alcohol_nystagmus	2021-01-18T18:57:40	{"wikidata": ["Q7233198"]}
Neonatal dermatomyositis is a very rare, secondary, neonatal autoimmune disease characterized by generalized weakness, severe hypotonia, absent or reduced deep tendon reflexes, and highly elevated serum creatine kinase levels presenting in the neonatal period. Perifascicular atrophy in the presence of a diffuse perivascular inflammatory cell exudate is observed on muscle biopsy. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Neonatal dermatomyositis	None	3,989	orphanet	https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=398117	2021-01-23T18:18:47	{"icd-10": ["M33.1"], "synonyms": ["Neonatal DM"]}
This article relies too much on references to primary sources. Please improve this by adding secondary or tertiary sources. (May 2019) (Learn how and when to remove this template message) Periapical granuloma,[1] also sometimes referred to as a radicular granuloma or apical granuloma, is an inflammation at the tip of a dead (nonvital) tooth. It is a lesion or mass that typically starts out as an epithelial lined cyst, and undergoes an inward curvature that results in inflammation of granulation tissue at the root tips of a dead tooth. This is usually due to dental caries or a bacterial infection of the dental pulp. Periapical granuloma is an infrequent disorder that has an occurrence rate between 9.3 to 87.1 percent.[2] Periapical granuloma is not a true granuloma due to the fact that it does not contain granulomatous inflammation; however, periapical granuloma is a common term used.[3] ## Contents * 1 Symptoms * 2 Radiographic Features * 3 Histopathology * 4 Treatment * 5 See also * 6 References ## Symptoms[edit] Patients who have a periapical granuloma are usually asymptomatic; however, when there is inflammation, patients could experience temperature sensitivity, pain while chewing solid foods, swelling and sensitivity to a dental percussion test.[4][better source needed] Generally, periapical granuloma is diagnosed due to acute pain in a tooth, or during a radiographic examination in routine visits to the dentist.[5][better source needed] ## Radiographic Features[edit] When looking at the radiographic features of periapical granuloma, typically there is a radiolucent lesion visible at the tip of a root on a nonvital tooth. This often is associated with root resorption. The radiolucency must correlate with the lateral root surface or the root of the tooth.[1] The average size of radiography when looking at periapical granuloma is 7.4 millimeters (mm).[6][non-primary source needed] ## Histopathology[edit] When examining the tissues of periapical granuloma for disease, hyperaemia, oedema and chronic inflammation is observed in the periodontal ligament. The vascular amplification and inflammation is adjacent to the bone, and bone absorption occurs next to a large growth in fibroblast and endothelial cells which is composed of the minute fibers (fibrils) with small vascular conduits (channels of passage for fluids).[7] The lesion is predominantly composed of plasma cells that are mixed with macrophages and lymphocytes with endothelial cells and fibroblasts.[8] ## Treatment[edit] Treatment for periapical granuloma is initially treated with a nonsurgical procedure. Endodontic treatments of teeth with periapical lesions (lesions that occurred as a result of dental pulp inflammation) have a success rate up to 85 percent.[9][non-primary source needed] Other forms of nonsurgical treatments used for periapical lesions are: a root canal, an aspiration-irrigation technique (a technique to help minimize the force required for the removal of root canal irrigant);[10][non-primary source needed] a decompression technique (a minimally invasive surgery that involves the placement of tubing to help maintain drainage);[11] Lesion Sterilization and Repair Therapy (a technique that allows disinfection of pulpal (dental pulp), dentinal (dentin) and periradicular (around a root) lesions by using a combination of antibacterial drugs;[12] a method using calcium hydroxide and the Apexum procedure (a minimally invasive removal, through a root canal access, of periapical chronically inflamed tissue).[13] It is essential to monitor the healing closely after treatment with frequent follow-up examinations. If nonsurgical techniques fail, surgical intervention is then recommended.[citation needed] There are many things to be considered prior to surgical treatment in order to decide which technique will have the best outcome. When determining an approach for surgical approaches, clinicians must establish the correct diagnosis of the lesion to make sure there isn’t treatment being done on healthy (vital) teeth. It is also important to take into consideration the distance (proximity) of the lesion to the vital teeth. If the lesion is in close proximity to the roots of vital teeth, a surgical approach may have negative outcomes that include the blood vessels and nerves of the adjacent teeth being injured, this of which would jeopardize their vitality (life). Surgical approaches increase the risk of the anatomic structures being damaged. Some of these anatomic structures include: the nasal cavity, mental foramen, the inferior alveolar nerve and / or the inferior alveolar artery and the maxillary sinus. When sinus cavities or adjacent tissue spaces are involved, the nonsurgical aspiration-irrigation technique is also not advised. The patient’s cooperation and age of the patient are very important as well. Patients may experience pain or discomfort during or after treatment when taking the surgical approach which could make them uncooperative. Patients that are older may not be able to tolerate this pain or discomfort, therefore they may require nonsurgical approaches. If access to the apical foramen is prevented due to blockages in the root canal system, a surgical approach may be warranted. Finally, surgery is recommended in cases where patients have the presence of cholesterol crystals or inflammatory apical true cysts (the top of an enclosed space lined by the epithelium and usually contains fluid)[14] due to the fact that these can prevent the healing of the lesions.[2] ## See also[edit] * Periapical periodontitis ## References[edit] 1. ^ a b Flucke U, Thompson LD (2019). "Non-Neoplastic Lesions of the Gnathic Bones". Head and Neck Pathology (Third ed.). pp. 363–382. doi:10.1016/b978-1-4377-2607-7.00022-1. ISBN 9781437726077. 2. ^ a b Fernandes M, de Ataide I (October 2010). "Nonsurgical management of periapical lesions". Journal of Conservative Dentistry. 13 (4): 240–5. doi:10.4103/0972-0707.73384. PMC 3010029. PMID 21217952. 3. ^ Neville BW, Damm DD, Allen CA, Bouquot JE (2002). Oral & maxillofacial pathology (2nd ed.). Philadelphia: W.B. Saunders. pp. 113–124. ISBN 978-0721690032.CS1 maint: uses authors parameter (link) 4. ^ Bahcall, J. "A Clinician's Guide to Clinical Endodontics : Percussion Tests for Determining the Status of the Periodontal Ligament". p. 6. 5. ^ Cleveland Clinic. (2017, January 26). Acute Pain vs. Chronic Pain. Retrieved from https://my.clevelandclinic.org/health/articles/12051-acute-vs-chronic-pain 6. ^ Farhadi F, Mirinezhad SS, Zarandi A (2016). "Using Periapical Radiography to Differentiate Periapical Granuloma and Radicular Cysts". Avicenna Journal of Dental Research. 8 (2). doi:10.17795/ajdr-30882. Archived from the original on 2018-04-10. 7. ^ Bajaj A (May 17, 2018). "Acme, Pathosis, Furuncle: The Periapical Granuloma. Retrieved from". Journal of Gastrointestinal Disorders and Liver Function. 4 (1): 11–13. doi:10.15436/2471-0601.18.1885. 8. ^ "Periapical granuloma". World Health Organization. 9. ^ Akinyamoju AO, Gbadebo SO, Adeyemi BF (December 2014). "Periapical lesions of the jaws: a review of 104 cases in ibadan". Annals of Ibadan Postgraduate Medicine. 12 (2): 115–9. PMC 4415388. PMID 25960702. 10. ^ Fukumoto Y (March 2005). "[Intracanal aspiration technique for root canal irrigation: evaluation of smear layer removal]". Kokubyo Gakkai Zasshi. The Journal of the Stomatological Society, Japan. 72 (1): 13–8. doi:10.5357/koubyou.71and72.13. PMID 15856767. 11. ^ Fernandes M, De Ataide I (June 2010). "Non-surgical management of a large periapical lesion using a simple aspiration technique: a case report". International Endodontic Journal. 43 (6): 536–42. doi:10.1111/j.1365-2591.2010.01719.x. PMID 20536582. 12. ^ Anila B, Murali H, Cheranjeevi H, Kapil RS (2014). "Lesion Sterilization and Tissue Repair (LSTR): A Review" (PDF). Journal of Scientific Dentistry. 4 (2): 49–55. 13. ^ Raisingani D (2011). "Apexum: A Minimum Invasive Procedure". International Journal of Clinical Pediatric Dentistry. 4 (3): 224–7. doi:10.5005/jp-journals-10005-1113. PMC 5034082. PMID 27678230. 14. ^ Holm N (August 27, 2018). "Cutaneous Columnar Cysts". Medscape. [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Periapical granuloma	c0031029	3,990	wikipedia	https://en.wikipedia.org/wiki/Periapical_granuloma	2021-01-18T19:02:13	{"mesh": ["D010484"], "umls": ["C0031029"], "icd-9": ["522.6"], "icd-10": ["K04.5"], "wikidata": ["Q3775782"]}
Genital-related neurosis, in which an individual has an overpowering belief that his or her genitalia are retracting and will disappear, despite the lack of any true longstanding changes to the genitals Not to be confused with Kuru (disease). Koro Other namesGenital retraction syndrome, shrinking penis SpecialtyPsychiatry Koro is a culture-bound syndrome delusional disorder in which an individual has an overpowering belief that his or her sex organs are retracting and will disappear, despite the lack of any true longstanding changes to the genitals.[1][2] Koro is also known as shrinking penis, and it is listed in the Diagnostic and Statistical Manual of Mental Disorders. The syndrome occurs worldwide, and mass hysteria of genital-shrinkage anxiety has a history in Africa, Asia and Europe.[3] In the United States and Europe, the syndrome is commonly known as genital retraction syndrome.[4] The condition can be diagnosed through psychological assessment along with physical examination to rule out genuine disorders of the genitalia that could be causing true retraction.[5][6] The word was borrowed from Malay and means the head of a turtle (or tortoise), referring to how it looks when they retract their heads into their shells.[7][8] ## Contents * 1 Signs and symptoms * 2 Causes * 3 Diagnosis * 3.1 History and physical examination * 3.2 Classification * 3.3 Differential diagnosis * 4 Treatment * 4.1 Indigenous treatment * 5 Epidemiology * 5.1 China * 5.2 Southeast Asia * 5.3 Africa * 5.4 US and Europe * 6 Society and culture * 6.1 Chinese cultural beliefs * 6.2 Etymology and geographical background * 7 See also * 8 References * 9 Further reading * 10 External links ## Signs and symptoms[edit] Most patients report acute anxiety attacks due to perceived genital retraction and/or genital shrinkage, despite a lack of any objectively visible biological changes in the genitalia that are longstanding. "Longstanding" refers to changes that are sustained over a significant period and do not appear reversible, unlike the effect of cold temperatures on some genital regions that cause retraction. These changes may trigger a koro attack when observed, although the effects of cold temperatures are objectively reversible.[9] According to literature, episodes usually last several hours, though the duration may be as long as two days.[7] There are cases in which koro symptoms persist for years in a chronic state, indicating a potential co-morbidity with body dysmorphic disorder.[10][11] In addition to retraction, other symptoms include a perception of alteration of penis shape and loss of penile muscle tone. In cases when sufferers have no perception of retraction, some patients may complain of genital paraesthesia or genital shortening.[12] Among females, the cardinal symptom is nipple retraction in the breast, generally into the breast as a whole.[10] Psychological components of koro anxiety include fear of impending death, penile dissolution and loss of sexual power.[10][13] Feelings of impending death along with retraction and perceived spermatorrhea has a strong cultural link with Chinese traditional beliefs. This is demonstrated by the fact that Asians generally believe koro symptoms are fatal, unlike most patients in the West.[10][14] Other ideational themes are intra-abdominal organ shrinkage, sex change to female or eunuch, non-specific physical danger, urinary obstruction, sterility, impending madness, spirit possession and a feeling of being bewitched.[10] Extremely anxious sufferers and their family members may resort to physical methods to prevent the believed retraction of the penis. A man may perform manual or mechanical penile traction, or "anchoring" by a loop of string or some clamping device.[15] Similarly, a woman may be seen grabbing her own breast, pulling her nipple, or even having iron pins inserted into the nipple.[14] Physical injury may occur from these attempts.[10] These forceful attempts often lead to injuries, sometimes death.[16] ## Causes[edit] Psychosexual conflicts, personality factors, and cultural beliefs are considered as being of etiological significance to koro.[17] Sexual adjustment histories of non-Chinese victims are often significant, such as premorbid sex inadequacy, sexual promiscuity, guilt over masturbation, and impotence.[18] ## Diagnosis[edit] Several criteria are typically used to make a diagnosis of koro. The primary criteria is a patient's report of genital (typically penile or female nipple) retraction despite a lack of objective physical evidence demonstrating retraction. This is accompanied by severe anxiety related to the retraction, fear of death as a result of retraction, and use of mechanical means to prevent retraction.[19] Cases that do not meet all the requirements are generally classified as koro-like symptoms or given a diagnosis of partial koro syndrome.[19] It has been argued that the criteria are sufficient but not necessary to make a diagnosis of koro.[10] Researchers have identified koro as a possible "cultural relative" of body dysmorphic disorder. DSM-IV explains the process of differential diagnosis between these two disorders.[11] ### History and physical examination[edit] A medical, psychosexual and psychiatric history should be documented. The physician should explore the patient’s concerns about appearance and body image (ruling out body dysmorphic disorder). Additionally, the physician should inquire about overall beliefs, personal values, and assumptions that the patient is making about his or her genitals. Given that koro is often an “attack” with a great deal of associated anxiety, the physician should ascertain the patient’s emotional state along with the timeline from onset to the presentation at the examination.[20][21][22] A physical examination should involve an assessment of overall health along with a detailed genital examination. In men, genital examination should be performed immediately after penile exposure, to avoid changes due to external temperature. The primary intent of the male exam is to exclude genuine penile anomalies such as hypospadias, epispadias and Peyronie's disease.[5][21] The presence of a significant suprapubic fat pad should be noted as well.[23] Careful measurements of flaccid length, stretched length and flaccid girth will also be useful. If male patients insist that their penis is shrinking and disappearing,[5] measurements after intracavernosal alprostadil may be used in the office to determine the true erect length and to diagnose any penile abnormalities in the erect state.[21] A physical examination should note any injuries inflicted by the patient in an effort to "prevent" retraction as further confirmation of koro.[5] ### Classification[edit] In DSM-IV-TR, koro is listed as one of the entries in the Glossary of Culture-Bound Syndromes of Appendix I. The manual gives koro's definition as "a term, probably of Malaysian origin, that refers to an episode of sudden and intense anxiety that the penis (or, in females, the vulva and nipples) will recede into the body and possibly cause death."[1] Attempts have been made by numerous authors to place koro into different classes. For example, koro may fit into the group of "specific culture-imposed nosophobia" (classification with cardinal sign),[24] "the genital retraction taxon" (classification with common factors between syndromes),[25] and the group with "culture-related beliefs as causes for the occurrence" (classification according to how the syndromes might be affected by cultural factors).[26] Various authors have attempted to distinguish between complete and incomplete forms of koro, along with cultural and non-cultural forms.[17] Cultural forms are said to involve a cultural belief or myth which plays a role in the genesis and spread of the disease in the community. These are regarded as complete forms of koro, matching all the symptoms required for diagnosis without significant co-morbidity.[17][10] Differentiation into primary koro, a culture-bound expression, and secondary koro. Secondary koro is proposed to have co-morbidity with a CNS disorder, another psychiatric disorder, or possible drug use.[10] Traditional Chinese medicine recognises koro as a sexual disease and classifies it into two categories, namely "cold conglomeration in liver" and "depletion of kidney's yang".[27] ### Differential diagnosis[edit] Men who present with this complaint may have koro, but they may also be misinformed about normal genital size.[6] Additionally, they may be suffering from penile dysmorphophobia.[28] Penile dysmorphophobia is related to body dysmorphic disorder (BDD), defined by the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (Text Revision) (DSM-IV-TR) as a condition marked by excessive preoccupation with an imaginary or minor defect in a facial feature or localized part of the body. BDD is different from koro. In koro, a patient is overcome with the belief that his penis is actively shrinking, and it may be in imminent danger of disappearing.[29] Clinical literature indicates that these two psychological conditions should be separated during differential diagnosis.[6] In addition to differentiating koro from body dysmorphic disorder, physicians also recommend that differential diagnosis separates koro from physical urological abnormalities.[5][6][30] For example, one physical disorder that causes loss of penile size is Peyronie's disease, where the tunica albuginea develops scar tissue that prevents the full expansion of an erection and causes flaccid penis retraction.[31][32] Additionally, a buried penis is a normally developed penis, partially covered by the suprapubic fat which can be surgically removed.[6][23] ## Treatment[edit] In historical culture-bound cases, reassurance and talks on sexual anatomy are given.[15] Patients are treated with psychotherapy distributed according to symptoms and to etiologically significant points in the past. Prognosis appears to be better in cases with a previously functional personality, a short history and low frequency of attacks, and a relatively uncomplicated sexual life.[7] For sporadic Western cases, careful diagnostic workup including searching for underlying sexual conflict is common. The choice of psychotherapeutic treatment is based on the psychiatric pathology found.[33][34] ### Indigenous treatment[edit] In China, traditional treatment based on the causes suggested by cultural beliefs are administrated to the patient. Praying to gods and asking Taoist priests to perform exorcism is common. If a fox spirit is believed to be involved, people may hit gongs or beat the person to drive it out. The person will receive a yang- or yin-augmenting Chinese medicine potion, usually including herbs, pilose antler (stag of deer) or deer tail, and tiger penis, deer penis, or fur seal penis. Other foods for therapy are pepper soup, ginger soup and liquor.[14] ## Epidemiology[edit] Among the Chinese, koro is confined to South China and the lower Yangtze Valley.[7] A 1992 study of self-report questionnaires suggests that in the epidemic area of China, koro victims are mostly Han, male, young, single, poorly educated and fearful of supernatural forces and koro.[14] The phenomenon is also found among oversea Chinese in Southeast Asia, especially Malaysia and Indonesia, and less frequently among the Malay and Indonesian inhabitants of the countries.[7] Though there are speculations that the occurrence of koro among people in Malaysia and Indonesia was the result of Chinese migrants, this cultural diffusion view is challenged since koro epidemics have been reported in Thailand and India, involving masses of non-Chinese people.[35] Sporadic cases of koro among people with non-Southeast-Asian ethnicity have been reported across the globe, for example, Nepali,[36] Sudanese,[37] Jordanian,[38] Tanzanian,[39] Nigerian,[40] French,[41] British,[42][43][44] American[45][46] and Canadian.[47][48] In most of the non-Chinese cases in the Western hemisphere, genital shrinkage is reported but not all the other typical koro symptoms, such as fear of death, as in endemic countries.[49] The incomplete forms of koro are regarded as the non-cultural forms, while the complete form with acute anxiety is the classical culture-bound type.[17] ### China[edit] Local official records indicate genital retraction epidemics in Hainan Island and Leizhou Peninsula in Guangdong, China, as early as the late nineteenth century. There were a series of epidemic outbursts in 1948, 1955, 1966, and 1974, whenever there was social tension or impending disaster, followed by the last widespread episode in 1984–1985 and a much smaller outbreak in 1987. The 1984–1985 epidemics lasted for over a year and affected over 3,000 people in 16 cities and provinces. A mental health campaign was conducted for the epidemic and since then no further episodes of the epidemic has occurred in China. Improvement in local economic conditions, associated with a better quality of life, is suggested to contribute to the fading of the episodic occurrences of koro.[14][35] ### Southeast Asia[edit] A koro epidemic struck Singapore in October 1967 for about ten days. Newspapers initially reported that some people developed koro after eating the meat of pigs inoculated with a vaccine for swine influenza. Rumours relating eating pork and koro spread after a further report of an inoculated pig dying from penile retraction. The cases reported amounted to 97 in a single hospital unit within one day, at five days after the original news report. Government and medical officials alleviated the outbreak only by public announcements over television and in the newspapers.[50][51][52] An epidemic outbreak in November 1976 in Isan, Thailand caused at least 350 cases, most of them Thai and males. Popular opinion and news media echoed the victims' projection of viewing the epidemic as caused by Vietnamese food and tobacco poisoning in a hideous assault against the Thai people.[53][54] Another large-scale epidemic in Thailand occurred in 1982.[53] In 1982, a koro epidemic episode in Northeast India affected, in majority, poorly educated people from lower socio-economic strata. There was no evidence of significant premorbid or sexual psychopathology in most cases.[55] Mass Koro epidemic was reported in Labour Camps in Kochi, Kerala in South India during August and September 2010 among migrant labour population from North and North-east India. Reportedly, the epidemic spread to about 100 individuals in 3 labour Camps within 2 weeks. ### Africa[edit] In the 1970s and early 1980s, newspapers reported incidents of genital shrinking in Western Nigeria. Since late 1996, a small-scale epidemic of genital shrinking was reported in West African nations. Victims in the African outbreaks often interpreted the experience as genital theft, accusing someone with whom they had contact of "stealing" the organ and the spiritual essence, causing impotence. The perceived motive for theft was associated with local occult belief, the witchcraft of juju, to feed the spiritual agency or to hold the genital for ransom. Social representations about juju constitute consensual realities that propose both a means and motivation for genital-shrinking experience.[19] The epidemic began in Nigeria and Cameroon, and spread to Ghana, Ivory Coast and Senegal by 1997.[19] Cases were reported in Cotonou, Benin where mobs attacked individuals accused of the penis theft and authorities ordered security forces to curb the violence, following the deaths of five people by vigilantes.[56] Later reports of outbreak suggest a spread beyond West Africa, including the coverage of episodes in Khartoum, Sudan in September 2003; Banjul, Gambia in October 2003;[19] and Kinshasa, DR Congo in 2008.[57] Comparing West African genital-shrinking epidemics with koro in Southeast Asia, the latter has symptoms centered on genital retraction (instead of shrinkage) and fear of death (which is absent in African cases).[19] A study analyzing the West African epidemics from 1997 to 2003 concluded that rather than psychopathology, the episodes were product of normal psychological functioning in undisturbed individuals, who were influenced by the local cultural models or social representations.[19] ### US and Europe[edit] In the late Middle Ages in Europe, it was believed that men could lose their penises through magical attacks by witches.[3] The Malleus Maleficarum, a fifteenth-century European manual for witchcraft investigations, relates stories of men claiming that their genitals had disappeared, being "hidden by the devil … so that they can be neither seen nor felt." They were said to have reappeared after the men had appeased the witches responsible.[58] Witches were said to store the removed genitals in birds' nests or in boxes, where "they move themselves like living members and eat oats and corn".[58] At least three publications of the 1880s, from US, Russia and England, reported genital retraction pathology, without using the Malay or Chinese term. Koro epidemics in China were first noticed in a French report in 1908 and descriptions of koro entered clinical books of western medicine in 1936. In the 1950s, koro is noted in nosological and diagnostic psychiatry.[53] ## Society and culture[edit] ### Chinese cultural beliefs[edit] Most of the ancient literature concerning koro was related to Chinese ethnic groups. For example, koro (in its Chinese term of shuk yang, shook yong or suo yang (simplified Chinese: 缩阳; traditional Chinese: 縮陽)) is documented in the old medical book New Collection of remedies of value (simplified Chinese: 验方新篇; traditional Chinese: 驗方新篇) which was published in Qing Dynasty. The book described the condition as "yin type of cold qi invasion" (simplified Chinese: 阴症伤寒; traditional Chinese: 陰症傷寒) which involved a sudden seizure during sexual intercourse with the penis retracting into the abdomen. It asserts that the patient will die if not treated with "heaty" drugs in time.[15] Factors of cultural expectation in the genesis of koro can be built upon ideas of sex physiology in the traditional Chinese medicine, with free play of imagination which links fatality with genital retraction.[15] In the ancient Chinese medical book Zhong Zang Jing (simplified Chinese: 中藏经; traditional Chinese: 中藏經), retraction of the penis with distension of the abdomen was described as a certain sign of death.[15] The yin and yang theory proposes that an unbalanced loss of the yang humour produces genital shrinkage.[7] In Taoism and traditional Chinese medicine, frequent ejaculation is regarded as detrimental to health, as semen is considered to be related to a man's vital energy, and hence excessive depletion of semen may lead to illness or death. Some authors believe that the idea of death caused by the semen depletion resembles the idea of death caused by genital disappearance, although such linkage between koro and Taoism, which influences Chinese medicine to some degree, is only speculative.[14] The popularity of Chinese folklore also plays a role. The novel about ghost stories Strange Stories from a Chinese Studio describes a fox spirit which can make people weak physically and sexually and shrink their tissues. Belief in koro being caused by the fox ghost among the southern Chinese has been reported.[14] ### Etymology and geographical background[edit] The earliest Western reference to the term koro is found in B.F. Matthes' Dictionary of Buginese Language (1874) of South Sulawesi, Indonesia.[53] The name could be derived from a river, its surrounding valley, and a local tribe of the same name which is located at northwestern sector of Sulawesi, Indonesia.[59] The word is also used in Makassarese language, meaning "to shrink"; the full expression is garring koro.[10] Koro may also be derived from Malay term Kura which means "head of turtle"[59][14] or keruk which means "to shrink".[60] The term shuk yang (缩阳), adapted from Chinese, means "the shrinkage of penis".[14] The term koro is also known as rok loo (genital shrinkage disease) in Thailand, jinjinnia bemar in Assam, India, and lanuk e laso by Bogoba tribe in Philippines.[59] ## See also[edit] * Shenkui, a similar Chinese culture-bound syndrome * Castration anxiety * Culture-bound syndrome * Diagnostic and Statistical Manual of Mental Disorders * Traditional Chinese Medicine * Mental health in China ## References[edit] 1. ^ a b American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision. American Psychiatric Pub. pp. 898–901. ISBN 978-0-89042-025-6. 2. ^ "Koro". dictionary.com. Retrieved 1 April 2013. 3. ^ a b Mattelaer, Johan J.; Jilek, Wolfgang (2007). "Koro?The Psychological Disappearance of the Penis". The Journal of Sexual Medicine. 4 (5): 1509–1515. doi:10.1111/j.1743-6109.2007.00586.x. ISSN 1743-6095. PMID 17727356. 4. ^ "Top 10 Little-Known Mental Disorders". Discovery Communications. Retrieved 15 July 2012. 5. ^ a b c d e Chowdhury, Arabinda N. (March 1996). "The definition and classification of Koro". Culture, Medicine and Psychiatry. 20 (1): 41–65. doi:10.1007/bf00118750. PMID 8740958. 6. ^ a b c d e Ghanem, Hussein; Glina, Sidney; Assalian, Pierre; Buvat, Jacques (January 2013). "Position Paper: Management of Men Complaining of a Small Penis Despite an Actually Normal Size". The Journal of Sexual Medicine. 10 (1): 294–303. doi:10.1111/j.1743-6109.2012.02725.x. PMID 22512935. 7. ^ a b c d e f Yap, Pow-Meng (1965), "Koro – A Culture-Bound Depersonalization Syndrome", British Journal of Psychiatry, 111 (470): 45–50, doi:10.1192/bjp.111.470.43, ISSN 0007-1250, PMID 14261727 8. ^ Gorvett, Zaria. "What we can learn from 'untranslatable' illnesses". www.bbc.com. Retrieved 9 June 2020. 9. ^ Ngui, P. W. (1969), "The Koro Epidemic in Singapore", Australian and New Zealand Journal of Psychiatry, 3 (3a (special issue on studies of anxiety)): 263–6, ISSN 0004-8674 10. ^ a b c d e f g h i j Chowdhury, Arabinda N. (March 1996), "The definition and classification of Koro", Culture, Medicine and Psychiatry, 20 (1): 41–65, doi:10.1007/bf00118750, ISSN 0165-005X, PMID 8740958 11. ^ a b https://web.archive.org/web/20100705184318/http://www.dsm5.org/research/documents/phillips_bdd.pdf 12. ^ Chowdhury, Arabinda N. (1992), "Clinical Analysis of 101 Koro Cases", Indian Journal of Social Psychiatry, 8: 67–70 13. ^ Mattelaer, J. and Jilek, W. (2007, September). Koro—The psychological disappearance of the penis. Retrieved 5 March 2013, from Ebscohost Database.[1][permanent dead link] 14. ^ a b c d e f g h i Cheng, Sheung-Tak (March 1996), "A Critical Review of Chinese Koro", Culture, Medicine and Psychiatry, 20 (1): 41–65, doi:10.1007/BF00118751, ISSN 0165-005X, PMID 8740959 15. ^ a b c d e Gwee, Ah Leng (1963), "Koro – A Cultural Disease", Singapore Medical Journal, 4: 119–22 16. ^ Garlipp, Petra (2008), "Koro – a Culture-Bound Phenomenon Intercultural Psychiatric Implications", German Journal of Psychiatry, 11: 21–8, ISSN 1433-1055 17. ^ a b c d Adeniran, R. A.; Jones, J. R. (April 1994), "Koro: Culture-Bound Disorder or Universal Symptom?", British Journal of Psychiatry, 164 (4): 559–61, doi:10.1192/bjp.164.4.559, ISSN 0007-1250, PMID 8038952 18. ^ Berrios, G. E.; Morley, S. (September 1984), "Koro-like Symptoms in Non-Chinese Subjects", British Journal of Psychiatry, 145 (3): 331–4, doi:10.1192/bjp.145.3.331, ISSN 0007-1250, PMID 6478129 19. ^ a b c d e f g Dzokkoto, Vivian Afi; Adams, Glenn (2005), "Understanding genital-shrinking epidemics in West Africa : koro, juju or mass psychogenic illness?", Culture, Medicine and Psychiatry, 29 (3): 53–78, doi:10.1007/s11013-005-4623-8, ISSN 0165-005X, PMID 16108203 20. ^ Berrios GE, Morley SJ (1984). "Koro-like symptom in a non-Chinese subject". Br J Psychiatry. 145 (3): 331–4. doi:10.1192/bjp.145.3.331. PMID 6478129. 21. ^ a b c Wylie K. R., Eardley I. (2007). "Penile size and the 'small penis syndrome'". BJU International. 99 (6): 1449–1455. doi:10.1111/j.1464-410x.2007.06806.x. PMID 17355371. 22. ^ Jilek WG, Jilek-Aall L (1977). "A koro epidemic in Thailand". Transcult Psychiatr Res Rev. 14: 57–9. doi:10.1177/136346157701400110. 23. ^ a b Elder JS. Congenital anomalies of the genitalia. In:Walsh PC, Retik AB, Walsh PC, Campbell MF, eds. Campell’s urology. Philadelphia, London, Toronto: W.B. Saunders Comp.; 1998: 2120–43. 24. ^ Yap, Pow-Meng (1967), "Classification of the Culture-Bound Reactive Syndromes", Australian and New Zealand Journal of Psychiatry, 1 (4): 172–9, doi:10.3109/00048676709159191, ISSN 0004-8674 25. ^ Simons, Ronald C.; Hughes, Charles C. (1985). The Culture-bound syndromes: Folk Illnesses of Psychiatric and Anthropological Interest. Dordrecht, Holland: D. Reidel Publishing Company. pp. 485–6. ISBN 90-277-1858-X. 26. ^ Tseng, Wen-Shing (2001), Handbook of Cultural Psychiatry, San Diego: Academic press, ISBN 0-12-701632-5 27. ^ Wang, Minghui; Wang, Fenglei (March 2002), "Conceptualisation and treatment of koro in traditional Chinese medicine", The Chinese Journal of Human Sexuality (in Chinese), 11 (1): 559–61, ISSN 1672-1993 28. ^ Spyropoulos E, Christoforidisb C, Borousasa D, Mavrikosa S, Bourounisa M, Athanasiadisa S (2005). "Augmentation phalloplasty surgery for penile dysmorphophobia in young adults: Considerations regarding patient selection, outcome evaluation and techniques applied". Eur Urol. 48 (1): 121–8. doi:10.1016/j.eururo.2005.02.021. PMID 15967261. 29. ^ Ang PC, Weller MP (1984). "Koro and psychosis". Br J Psychiatry. 145 (3): 335. doi:10.1192/bjp.145.3.335. PMID 6478130. 30. ^ Kim J, Kim M, Lee N, Park Y (2000). "A case of urethrocutaneous fistula with the koro syndrome". J Urol. 164: 123. doi:10.1016/s0022-5347(05)67465-4. 31. ^ Brock Gerald; et al. (1997). "The anatomy of the tunica albuginea in the normal penis and Peyronie's disease". The Journal of Urology. 157 (1): 276–281. doi:10.1016/s0022-5347(01)65359-x. 32. ^ Greenfield Jason M.; Lucas Steven; Levine Laurence A. (2006). "Factors affecting the loss of length associated with tunica albuginea plication for correction of penile curvature". The Journal of Urology. 175 (1): 238–241. doi:10.1097/00005392-200601000-00078. 33. ^ Fishbain, D., Barsky, S., and Goldberg, M. (January, 1989). "Koro" (genital retraction syndrome): Psychotherapeutic interventions. Retrieved 25 March 2013, from EBSCOhost. [2][permanent dead link] 34. ^ Fishbain, David A.; Barsky, Steve; Goldberg, Myron (January 1989), "'Koro' (Genital Retraction Syndrome): Psychotherapeutic Interventions", American Journal of Psychotherapy, 43 (1): 87–91, doi:10.1176/appi.psychotherapy.1989.43.1.87, ISSN 0002-9564, PMID 2929797 35. ^ a b Tseng, W. S. (December 2006), "From Peculiar Psychiatric Disorders through Culture-bound Syndromes to Culture-related Specific Syndromes", Transcultural Psychiatry, 43 (4): 554–576, doi:10.1177/1363461506070781, PMID 17166946 36. ^ Chowdhury, A. N.; Rajbhandari, K. C. (1994), "Koro with Depression in Nepal", Transcultural Psychiatric Research Review, 32: 87–90, doi:10.1177/136346159503200108 37. ^ Baasher, T. A. (1963), "The Influence of Culture on Psychiatric Manifestation", Transcultural Psychiatric Research Review, 15: 51–2 38. ^ Al-Hmoud, N. (1999), "Koro-like syndrome in a Jordanian male", Eastern Mediterranean Health Journal, 5 (3): 611–3, PMID 10793842 39. ^ Lucieer, W. M. (1984), "The Bitter Taste of Liberty: A Study in Ethnopsychiatry", Psychopathologic Africane, 20: 17–40 40. ^ Ifabumunyi, O. I.; Rwegellera, G. G. C. (1979), "Koro in a Nigerian Male Patient: A Case Report", African Journal of Psychiatry, 5: 103–5 41. ^ Burgeois, M. (1896), "Un Koro Charentais (Transposition Ethnopsychiatrique)", Annales médico-psychologiques, 126: 749–51 42. ^ Barrett, K. (1978), "Koro in a Londoner", The Lancet, 8103 (2): 1319, doi:10.1016/s0140-6736(78)92093-7, PMID 82833 43. ^ Yap, Pow-Meng (August 1965), "Koro in a Briton", British Journal of Psychiatry, 111 (477): 774–5, doi:10.1192/bjp.111.477.774-a, ISSN 0007-1250 44. ^ Cremona, Anne (February 1981), "Another case of koro in a Briton", British Journal of Psychiatry, 138 (2): 180–1, doi:10.1192/bjp.138.2.180, ISSN 0007-1250, PMID 7260504 45. ^ Bychowski, G. (1952), Psychotherapy of Psychosis, New York: Grune and Stratton, pp. 109–10, hdl:2027/mdp.39015000915887 46. ^ Edwards, J. G. (1970), "The Koro pattern of depersonalization in an American schizophrenic patient", American Journal of Psychiatry, 126 (8): 1171–3, doi:10.1176/ajp.126.8.1171, PMID 5411375 47. ^ Dow, T. W.; Silver, D. (1973), "A drug induced Koro syndrome", Journal of Florida Medical Association, 60 (4): 32–3, PMID 4693685 48. ^ Ede, A. (1976), "Koro in an Anglo-Saxon Canadian", Canadian Psychiatric Association Journal, 21 (6): 389–92, doi:10.1177/070674377602100605, PMID 13924 49. ^ Kumar, H. V. (January 1987), "Koro in an Israeli Man", British Journal of Psychiatry, 150 (1): 133b, doi:10.1192/bjp.150.1.133b, ISSN 0007-1250, PMID 3651668 50. ^ Koro study team (December 1969), "The Koro "Epidemic" in Singapore", Singapore Medical Journal, 10 (4): 234–42, PMID 5371145 51. ^ Ng, B. Y. (August 1969), "History of Koro in Singapore", Singapore Medical Journal, 38 (8): 356–7, PMID 9364894 52. ^ Lee, Teh Jen (11 March 2012). "The year S'pore men feared for their penises". The New Paper. Archived from the original on 3 June 2015. Retrieved 3 June 2015. 53. ^ a b c d Chowdhury, Arabinda N. (September 1998), "Hundred Years of Koro: The History of a Culture-Bound Syndrome", The International Journal of Social Psychiatry, 44 (3): 181–8, doi:10.1177/002076409804400304, ISSN 0020-7640 54. ^ Jilek, W.; Jilel-Aall, L. (1977), "Mass-hysteria with Koro-symptoms in Thailand", Schweizer Archiv für Neurologie, Neurochirurgie und Psychiatrie, 120 (2): 257–9, PMID 905791 55. ^ Sachdev, P. S. (December 1985), "Koro Epidemic in North-East India", Australian and New Zealand Journal of Psychiatry, 19 (4): 433–8, doi:10.1080/00048678509158852, ISSN 0004-8674, PMID 3869009 56. ^ "Benin alert over 'penis theft' panic", BBC News, 27 November 2001, retrieved 26 January 2010 57. ^ Lynchings in Congo as penis theft panic hits capital, Reuters Africa, 23 April 2008, archived from the original on 11 May 2008, retrieved 2 May 2008 58. ^ a b Malleus Maleficarum Part II, Question I, Chapter VII 59. ^ a b c Durst, Rimona (1991). "The Disorder Named Koro" (PDF). Behavioural Neurology. 4 (1): 1–14. doi:10.1155/1991/525393. PMID 24487349. Retrieved 3 June 2015. 60. ^ Palthe, W. P. M. van (1934), "Koro, een Eigenaardige Angstneurose", Geneeskundig Tijdschrift voor Nederlandsch-Indie, 74: 1713–1720 ## Further reading[edit] * Cheng S.T. (1996). "A Critical Review of Chinese Koro". Culture, Medicine and Psychiatry. 20 (1): 67–82. doi:10.1007/bf00118751. PMID 8740959. * Michael W. Passer & Ronald E. Smith. "Sociocultural factors for Anxiety disorder". Psychology - The science of mind and behaviour (3rd ed.). p. 542.CS1 maint: uses authors parameter (link) * Ang, PC; Weller, MPI (September 1984). "Koro and psychosis". The British Journal of Psychiatry. Royal Medico-psychological Association. 145 (3): 335. doi:10.1192/bjp.145.3.335. ISSN 0007-1250. PMID 6478130. * Mattelaer, Johan J.; Jilek, Wolfgang (September 2007). "Koro—The Psychological Disappearance of the Penis". The Journal of Sexual Medicine. 4 (5): 1509–1515. doi:10.1111/j.1743-6109.2007.00586.x. PMID 17727356. * Frank Bures, "The Geography of Madness" (2016), Melville House Publishing, pp. 3-24, ISBN 9781612193724 ## External links[edit] Classification D * MeSH: D016911 * Koro Syndrome * Wall Street Journal's "Best of the Web Today," Wednesday, 22 October 2003 * Koro - the Genital Retraction Syndrome \- BBC h2g2, Page dedicated to Koro * A mind dismembered: In search of the magical penis thieves, Harper's Magazine, Frank Bures, June 2008. Authority control * LCCN: sh00009280 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Koro (medicine)	c0085429	3,991	wikipedia	https://en.wikipedia.org/wiki/Koro_(medicine)	2021-01-18T18:34:43	{"gard": ["11922"], "mesh": ["D016911"], "wikidata": ["Q1080699"]}
For a general description and a discussion of genetic heterogeneity of inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), see IBD1 (266600). Mapping In a genomewide linkage scan involving 282 IBD families of European descent, Hampe et al. (1999) identified a locus in the pericentromeric region of chromosome 10 defined by markers D10S547 and D10S20 that was associated with susceptibility to IBD with a maximum multipoint lod score of 2.30. In a panel of 1,182 individuals with Crohn disease and 2,024 controls, Parkes et al. (2007) analyzed 37 SNPs from 31 distinct loci that were associated at p values of less than 10(-5) in the Wellcome Trust Case Control Consortium (2007) dataset and obtained replication on chromosome 10q24 at rs10883365 (combined p = 3.71 x 10(-10)). Using an array custom-made for the Wellcome Trust Case Control Consortium (2007) and a staged experimental design, Fisher et al. (2008) genotyped a total of 3,133 unrelated patients with ulcerative colitis and 4,494 controls and obtained replication on chromosome 10q24 at rs10883365 (combined p = 2.4 x 10(-6)). Franke et al. (2008) investigated 50 previously reported susceptibility loci in a German sample of 1,850 CD patients, 1,103 UC patients, and 1,817 controls, and found association with rs11190140, located 1.1 kb upstream of the NKX2-3 gene (606727), for both CD (p = 8.87 x 10(-6)) and UC (p = 1.33 x 10(-8)). The authors noted that rs11190140 is in complete linkage disequilibrium with the lead SNP (rs10883365) from the Wellcome Trust Case Control Consortium (2007) study. In a metaanalysis of data from 3 studies of Crohn disease involving a total of 3,230 cases and 4,829 controls (Rioux et al., 2007, the Wellcome Trust Case-Control Consortium, 2007, and Libioulle et al., 2007) with replication in 3,664 independent cases, Barrett et al. (2008) confirmed significant association with rs11190140 at 10q24 (combined p = 3.06 x 10(-16); case-control odds ratio, 1.20). In a study involving 2,731 Dutch and Belgian IBD patients, including 1,656 CD patients and 1,075 UC patients, as well as 1,086 controls, Weersma et al. (2009) replicated association at rs10883365 for CD (corrected p = 2.36 x 10(-4)), but did not find significant association with UC. McGovern et al. (2010) combined new data from 2 genomewide association studies of ulcerative colitis involving 266,047 SNPs and performed a metaanalysis with previously published data (Silverberg et al., 2009), thus bringing together a discovery set of 2,693 European UC patients and 6,791 controls; the top results from the metaanalysis were then independently replicated with 2,009 additional European UC cases and 1,580 controls. McGovern et al. (2010) confirmed association with UC at rs11190140 (combined p = 1.1 x 10(-8)). ### Association with the DLG5 Gene Stoll et al. (2004) refined the previously defined linkage region on 10q23 and used positional cloning to identify genetic variants in the DLG5 gene (604090) associated with IBD. DLG5 encodes a scaffolding protein involved in the maintenance of epithelial integrity. They identified 2 distinct haplotypes with a replicable distortion in transmission in trios (both parents with 1 child). One of the risk-associated DLG5 haplotypes was distinguished from the common haplotype by a 113G-A SNP (rs1248696), resulting in an arg30-to-gln (R30Q) substitution in the DUF622 domain of DLG5 that was predicted to impede scaffolding of DLG5. They stratified the study sample according to the presence of risk-associated variants of CARD15 (3020insC, 605956.0001; G908R, 605956.0002; R702W, 605956.0003) to study potential gene-gene interaction and found a significant difference in association of the 113A variant of DLG5 with Crohn disease in affected individuals carrying the risk-associated CARD15 alleles versus those carrying non-risk-associated CARD15 alleles. This suggested a complex pattern of gene-gene interaction between DLG5 and CARD15, reflecting the complex nature of polygenic diseases. Friedrichs et al. (2006) observed a significant association between Crohn disease and the R30Q allele in the DLG5 gene in men (odds ratio = 2.49), but not in women (odds ratio = 1.01), among a cohort of 613 patients of German, Italian, and Canadian origin. The observed association was driven by a gender-dependent transmission ratio distortion of the R30Q allele in healthy controls that was absent in CD patients. In 461 healthy German adults, the frequency of the R30Q allele was 5.2% in men and 11.3% in women, but among 613 CD patients R30Q allele frequency was 10.1% in men and 10.9% in women. The finding was further substantiated in 601 Caucasian newborns in whom the frequency of the R30Q allele was 7.1% in males and 11% in females. Newman et al. (2006) genotyped a cohort of 402 Canadian Crohn disease and 179 ulcerative colitis patients and 537 healthy controls for 3 DLG5 variants previously associated with inflammatory bowel disease and Crohn disease. They found no relationship between the DLG5 variants studied and risk for IBD in the Ashkenazi Jewish subjects. Despite this and other caveats the data reported were thought to support the conclusion that DLG5 variants play a role in the pathogenesis of IBD. Browning et al. (2008) analyzed DLG5 R30Q genotype data from 11 earlier studies that did not include gender-stratified allele counts in the published reports. They found no male-female allele frequency differences in controls, and only marginal evidence that the 30Q allele is associated with a decreased risk of CD in women (p = 0.049; OR, 0.87). Combining their data with that of previously published gender-stratified data, Browning et al. (2008) concluded that the DLG5 30Q allele is associated with a small reduction in risk of CD in women (p = 0.010; OR, 0.86). [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: 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 20	c2676781	3,992	omim	https://www.omim.org/entry/612288	2019-09-22T16:01:59	{"mesh": ["C567361"], "omim": ["612288"]}
Malignant infantile osteopetrosis Other namesInfantile autosomal recessive osteopetrosis, Infantile osteopetrosis Malignant infantile osteopetrosis, is a rare osteosclerosing type of skeletal dysplasia that typically presents in infancy and is characterized by a unique radiographic appearance of generalized hyperostosis \- excessive growth of bone. The generalized increase in bone density has a special predilection to involve the medullary portion with relative sparing of the cortices.[1] Obliteration of bone marrow spaces and subsequent depression of the cellular function can result in serious hematologic complications. Optic atrophy and cranial nerve damage secondary to bony expansion can result in marked morbidity. The prognosis is extremely poor in untreated cases.[2] Plain radiography provides the key information to the diagnosis. Clinical and radiologic correlations are also fundamental to the diagnostic process, with additional gene testing being confirmatory. ## Contents * 1 Presentation * 2 Diagnosis * 2.1 Skeletal radiography * 2.2 Differential diagnosis * 3 Treatment * 4 References * 5 External links ## Presentation[edit] Hematologic manifestations related to bone marrow suppression and subsequent pancytopenia are a major source of morbidity and mortality. Additionally extramedullary hematopoiesis can result in liver and spleen dysfunction. Cranial nerve dysfunction and neurologic complications are usually associated with infantile osteopetrosis. Expansion of the skull bone leads to macrocephaly. Additionally, linear growth retardation that is not apparent at birth, delayed motor milestones and poor dentition can occur.[2] ## Diagnosis[edit] ### Skeletal radiography[edit] The generalized increase in bone density of the medullary portion predominates with relative sparing of the cortices. The axial and appendicular skeleton are uniformly involved. Malignant infantile osteopetrosis is known for exhibiting specific plain radiographic abnormalities:[1] * Loss of differentiation between the medullary and cortical portions of bone is a radiographic hallmark of infantile osteopetrosis * Characteristic endobone or “bone-within-bone” appearance in the spine, or “sandwich vertebra” appearance, characterized by dense endplate sclerosis with sharp margins * Characteristic endobone or “bone-within-bone” appearance in the pelvis and long bones of extremities where areas of osteosclerosis intermingle with areas of relatively hypodense bone. * Failure of remodeling of the distal femoral and proximal humeral metaphyses giving the affected bones a funnel shaped appearance known as (Erlenmeyer flask deformity) * Alternating radiolucent femoral metaphyseal bands * Pathologic fractures ### Differential diagnosis[edit] The differential diagnosis of malignant infantile osteopetrosis includes other genetic skeletal dysplasias that cause osteosclerosis. They are collectively known as osteosclerosing dysplasias. The differential diagnosis of genetic osteosclerosing dysplasias including infantile osteopetrosis has been tabulated[1] and illustrated in literature citations.[3] * Neuropathic infantile osteopetrosis * Infantile osteopetrosis with renal tubular acidosis * Infantile osteopetrosis with immunodeficiency * IO with leukocyte adhesion deficiency syndrome (LAD-III) * Intermediate osteopetrosis * Autosomal dominant osteopetrosis (Albers-Schonberg) * Pyknodysostosis (osteopetrosis acro-osteolytica) * Osteopoikilosis (Buschke–Ollendorff syndrome) * Osteopathia striata with cranial sclerosis * Mixed sclerosing bone dysplasia * Progressive diaphyseal dysplasia (Camurati–Engelmann disease) * SOST-related sclerosing bone dysplasias ## Treatment[edit] The only effective line of treatment for malignant infantile osteopetrosis is hematopoietic stem cell transplantation.[2][4][5] It has been shown to provide long-term disease-free periods for a significant percentage of those treated;.[2] It can impact both hematologic and skeletal abnormalities;[2][4] and has been used successfully to reverse the associated skeletal abnormalities.[4][5] Radiographs of at least one case with malignant infantile osteopetrosis have demonstrated bone remodeling and recanalization of medullar canals following hematopoietic stem cell transplantation. This favorable radiographic response could be expected within one year following the procedure[4][5] \- nevertheless, primary graft failure can prove fatal.[2] ## References[edit] 1. ^ a b c EL-Sobky TA, Elsobky E, Sadek I, Elsayed SM, Khattab MF (2016). "A case of infantile osteopetrosis: The radioclinical features with literature update'. Bone Rep. 4:11-16. doi:10.1016/j.bonr.2015.11.002. PMC 4926827. PMID 28326337 2. ^ a b c d e f Orchard PJ, Fasth AL, Le Rademacher J, et al (2015). "Hematopoietic stem cell transplantation for infantile osteopetrosis". Blood. 126:270–6. DOI: 10.1182/blood-2015-01-625541. PMC 4497967 PMID 26012570 3. ^ Ihde LL, Forrester DM, Gottsegen CJ, Masih S, Patel DB, Vachon LA, et al. (2011). "Sclerosing bone dysplasias: Review and differentiation from other causes of osteosclerosis". RadioGraphics. 31:7, 1865-82. DOI: https://dx.doi.org/10.1148/rg.317115093 4. ^ a b c d EL-Sobky TA, El-Haddad A, Elsobky E, Elsayed SM, Sakr HM (2017). “Reversal of skeletal radiographic pathology in a case of malignant infantile osteopetrosis following hematopoietic stem cell transplantation”. Egypt J Radiol Nucl Med. 48 (1):237–43. http://doi.org/10.1016/j.ejrnm.2016.12.013. 5. ^ a b c Costelloe CM, Eftekhari F, Petropoulos D (2007). "Radiography of successful bone marrow transplantation for osteopetrosis". Skeletal Radiol. 36:S34–S37. DOI: 10.1007/s00256-006-0141-1 ## External links[edit] Classification D * ICD-10: Q78.2 External resources * Orphanet: 667 [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Malignant infantile osteopetrosis	c1318518	3,993	wikipedia	https://en.wikipedia.org/wiki/Malignant_infantile_osteopetrosis	2021-01-18T18:53:53	{"umls": ["C1318518"], "orphanet": ["667"], "wikidata": ["Q24960517"]}
Disease characterized by the rapid swelling Angioedema Other namesAngiooedema, Quincke's edema, angioneurotic edema Allergic angioedema: this child is unable to open his eyes due to the swelling. SpecialtyAllergy and immunology, emergency medicine SymptomsArea of swelling[1] Usual onsetMinutes to hours[1] TypesHistamine mediated, bradykinin mediated[1] Risk factorsFamily history[2] Diagnostic methodBased on symptoms[2] Differential diagnosisAnaphylaxis, abscess, contact dermatitis[2] TreatmentIntubation, cricothyroidotomy[1] MedicationHistamine: antihistamines, corticosteroids, epinephrine[1] Bradykinin: C1 esterase inhibitor, ecallantide, icatibant, fresh frozen plasma[1] Frequency~100,000 per year (US)[1] Angioedema is an area of swelling of the lower layer of skin and tissue just under the skin or mucous membranes.[1][3] The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs.[1] Often it is associated with hives, which are swelling within the upper skin.[1][3] Onset is typically over minutes to hours.[1] The underlying mechanism typically involves histamine or bradykinin.[1] The version related to histamine is due to an allergic reaction to agents such as insect bites, foods, or medications.[1] The version related to bradykinin may occur due to an inherited problem known as C1 esterase inhibitor deficiency, medications known as angiotensin-converting enzyme inhibitors, or a lymphoproliferative disorder.[1] Efforts to protect the airway may include intubation or cricothyroidotomy.[1] Histamine-related angioedema can be treated with antihistamines, corticosteroids, and epinephrine.[1] In those with bradykinin-related disease a C1 esterase inhibitor, ecallantide, or icatibant may be used.[1] Fresh frozen plasma may be used instead.[1] In the United States the disease affects about 100,000 people a year.[1] ## Contents * 1 Signs and symptoms * 2 Diagnosis * 2.1 Acquired angioedema * 2.2 Hereditary angioedema * 3 Pathophysiology * 4 Management * 4.1 Allergic * 4.2 Drug induction * 4.3 Hereditary * 4.4 Acquired * 4.5 Prophylaxis * 5 History * 6 Epidemiology * 7 See also * 8 References * 9 External links ## Signs and symptoms[edit] Angioedema of half of the tongue Angioedema of the face, most strikingly in the upper lip. The skin of the face, normally around the mouth, and the mucosa of the mouth and/or throat, as well as the tongue, swell over the period of minutes to hours. The swelling can also occur elsewhere, typically in the hands. The swelling can be itchy or painful. There may also be slightly decreased sensation in the affected areas due to compression of the nerves. Urticaria (hives) may develop simultaneously. In severe cases, stridor of the airway occurs, with gasping or wheezy inspiratory breath sounds and decreasing oxygen levels. Tracheal intubation is required in these situations to prevent respiratory arrest and risk of death. Sometimes, the cause is recent exposure to an allergen (e.g. peanuts), but more often it is either idiopathic (unknown) or only weakly correlated to allergen exposure. In hereditary angioedema (HAE), often no direct cause is identifiable, although mild trauma, including dental work and other stimuli, can cause attacks.[4] There is usually no associated itch or urticaria, as it is not an allergic response. Patients with HAE can also have recurrent episodes (often called "attacks") of abdominal pain, usually accompanied by intense vomiting, weakness, and in some cases, watery diarrhea, and an unraised, nonitchy splotchy/swirly rash. These stomach attacks can last one to five days on average and can require hospitalization for aggressive pain management and hydration. Abdominal attacks have also been known to cause a significant increase in the patient's white blood cell count, usually in the vicinity of 13,000 to 30,000. As the symptoms begin to diminish, the white count slowly begins to decrease, returning to normal when the attack subsides. As the symptoms and diagnostic tests are almost indistinguishable from an acute abdomen (e.g. perforated appendicitis) it is possible for undiagnosed HAE patients to undergo laparotomy (operations on the abdomen) or laparoscopy (keyhole surgery) that turns out to have been unnecessary. HAE may also cause swelling in a variety of other locations, most commonly the limbs, genitals, neck, throat and face. The pain associated with these swellings varies from mildly uncomfortable to agonizing pain, depending on its location and severity. Predicting where and when the next episode of edema will occur is impossible. Most patients have an average of one episode per month, but there are also patients who have weekly episodes or only one or two episodes per year. The triggers can vary and include infections, minor injuries, mechanical irritation, operations or stress. In most cases, edema develops over a period of 12–36 hours and then subsides within 2–5 days. ## Diagnosis[edit] The diagnosis is made on the clinical picture. Routine blood tests (complete blood count, electrolytes, kidney function, liver enzymes) are typically performed. Mast cell tryptase levels may be elevated if the attack was due to an acute allergic (anaphylactic) reaction. When the patient has been stabilized, particular investigations may clarify the exact cause; complement levels, especially depletion of complement factors 2 and 4, may indicate deficiency of C1-inhibitor. HAE type III is a diagnosis of exclusion consisting of observed angioedema along with normal C1 levels and function. The hereditary form (HAE) often goes undetected for a long time, as its symptoms resemble those of more common disorders, such as allergy or intestinal colic. An important clue is the failure of hereditary angioedema to respond to antihistamines or steroids, a characteristic that distinguishes it from allergic reactions. It is particularly difficult to diagnose HAE in patients whose episodes are confined to the gastrointestinal tract. Besides a family history of the disease, only a laboratory analysis can provide final confirmation. In this analysis, it is usually a reduced complement factor C4, rather than the C1-INH deficiency itself, that is detected. The former is used during the reaction cascade in the complement system of immune defense, which is permanently overactive due to the lack of regulation by C1-INH. Angioedema is classified as either hereditary or acquired. ### Acquired angioedema[edit] Acquired angioedema (AAE) can be immunologic, nonimmunologic, or idiopathic.[5] It is usually caused by allergy and occurs together with other allergic symptoms and urticaria. It can also occur as a side effect to certain medications, particularly ACE inhibitors. It is characterized by repetitive episodes of swelling, frequently of the face, lips, tongue, limbs, and genitals. Edema of the gastrointestinal mucosa typically leads to severe abdominal pain; in the upper respiratory tract, it can be life-threatening.[6] ### Hereditary angioedema[edit] Hereditary angioedema (HAE) exists in three forms, all of which are caused by a genetic mutation inherited in an autosomal dominant form. They are distinguished by the underlying genetic abnormality. Types I and II are caused by mutations in the SERPING1 gene, which result in either diminished levels of the C1-inhibitor protein (type I HAE) or dysfunctional forms of the same protein (type II HAE). Type III HAE has been linked with mutations in the F12 gene, which encodes the coagulation protein factor XII. All forms of HAE lead to abnormal activation of the complement system, and all forms can cause swelling elsewhere in the body, such as the digestive tract. If HAE involves the larynx, it can cause life-threatening asphyxiation.[7] The pathogenesis of this disorder is suspected to be related to unopposed activation of the contact pathway by the initial generation of kallikrein and/or clotting factor XII by damaged endothelial cells. The end product of this cascade, bradykinin, is produced in large amounts and is believed to be the predominant mediator leading to increased vascular permeability and vasodilation that induces typical angioedema "attacks".[8] ## Pathophysiology[edit] Bradykinin plays a critical role in all forms of hereditary angioedema.[9] This peptide is a potent vasodilator and increases vascular permeability, leading to rapid accumulation of fluid in the interstitium. This is most obvious in the face, where the skin has relatively little supporting connective tissue, and edema develops easily. Bradykinin is released by various cell types in response to numerous different stimuli; it is also a pain mediator. Dampening or inhibiting bradykinin has been shown to relieve HAE symptoms. Various mechanisms that interfere with bradykinin production or degradation can lead to angioedema. ACE inhibitors block ACE, the enzyme that among other actions, degrades bradykinin. In hereditary angioedema, bradykinin formation is caused by continuous activation of the complement system due to a deficiency in one of its prime inhibitors, C1-esterase (aka: C1-inhibitor or C1INH), and continuous production of kallikrein, another process inhibited by C1INH. This serine protease inhibitor (serpin) normally inhibits the association of C1r and C1s with C1q to prevent the formation of the C1-complex, which - in turn - activates other proteins of the complement system. Additionally, it inhibits various proteins of the coagulation cascade, although effects of its deficiency on the development of hemorrhage and thrombosis appear to be limited. The three types of hereditary angioedema are: * Type I - decreased levels of C1INH (85%); * Type II - normal levels, but decreased function of C1INH (15%); * Type III - no detectable abnormality in C1INH, occurs in an X-linked dominant fashion and therefore mainly affects women; it can be exacerbated by pregnancy and use of hormonal contraception (exact frequency uncertain).[10] It has been linked with mutations in the factor XII gene.[11] Angioedema can be due to antibody formation against C1INH; this is an autoimmune disorder. This acquired angioedema is associated with the development of lymphoma. Consumption of foods that are themselves vasodilators, such as alcoholic beverages or cinnamon, can increase the probability of an angioedema episode in susceptible patients. If the episode occurs at all after the consumption of these foods, its onset may be delayed overnight or by some hours, making the correlation with their consumption somewhat difficult. In contrast, consumption of bromelain in combination with turmeric may be beneficial in reducing symptoms.[12] The use of ibuprofen or aspirin may increase the probability of an episode in some patients. The use of acetaminophen typically has a smaller, but still present, increase in the probability of an episode. ## Management[edit] ### Allergic[edit] In allergic angioedema, avoidance of the allergen and use of antihistamines may prevent future attacks. Cetirizine is a commonly prescribed antihistamine for angioedema. Some patients have reported success with the combination of a nightly low dose of cetirizine to moderate the frequency and severity of attacks, followed by a much higher dose when an attack does appear. Severe angioedema cases may require desensitization to the putative allergen, as mortality can occur. Chronic cases require steroid therapy, which generally leads to a good response. In cases where allergic attack is progressing towards airway obstruction, epinephrine may be life-saving. ### Drug induction[edit] ACE inhibitors can induce angioedema.[13][14][15] ACE inhibitors block the enzyme ACE so it can no longer degrade bradykinin; thus, bradykinin accumulates and can cause angioedema.[13][14] This complication appears more common in African-Americans.[16] In people with ACE inhibitor angioedema, the drug needs to be discontinued and an alternative treatment needs to be found, such as an angiotensin II receptor blocker (ARB),[17] which has a similar mechanism but does not affect bradykinin. However, this is controversial, as small studies have shown some patients with ACE inhibitor angioedema can develop it with ARBs, as well.[18][19] ### Hereditary[edit] In hereditary angioedema (HAE), specific stimuli that have previously led to attacks may need to be avoided in the future. It does not respond to antihistamines, corticosteroids, or epinephrine. Acute treatment consists of C1-INH (C1-esterase inhibitor) concentrate from donor blood, which must be administered intravenously. In an emergency, fresh frozen blood plasma, which also contains C1-INH, can also be used. However, in most European countries, C1-INH concentrate is only available to patients who are participating in special programmes.[citation needed] The medications ecallantide and icatibant may be used to treat attacks.[1] In 2017 these medications cost between 5,700 and 14,000 US$ per dose in the United States, prices that tripled in two years.[20][medical citation needed] In those given icatibant, specialists monitor is recommended.[21] ### Acquired[edit] In acquired angioedema, HAE types I and II, and nonhistaminergic angioedema, antifibrinolytics such as tranexamic acid or ε-aminocaproic acid may be effective. Cinnarizine may also be useful because it blocks the activation of C4 and can be used in patients with liver disease, whereas androgens cannot.[22] ### Prophylaxis[edit] Future attacks of HAE can be prevented by the use of androgens such as danazol, oxandrolone or methyltestosterone. These agents increase the level of aminopeptidase P, an enzyme that inactivates kinins;[23] kinins (especially bradykinin) are responsible for the manifestations of angioedema. In 2018, the U.S. Food and Drug Administration approved lanadelumab, an injectable monoclonal antibody, to prevent attacks of HAE types I and II in people over age 12. Lanadelumab inhibits the plasma enzyme kallikrein, which liberates the kinins bradykinin and kallidin from their kininogen precursors and is produced in excess in individuals with HAE types I and II.[24][25] ## History[edit] Heinrich Quincke first described the clinical picture of angioedema in 1882,[26] though there had been some earlier descriptions of the condition.[27][28][29] William Osler remarked in 1888 that some cases may have a hereditary basis; he coined the term "hereditary angio-neurotic edema".[30] The link with C1 esterase inhibitor deficiency was proved in 1963.[31] ## Epidemiology[edit] There are as many as 80,000 to 112,000 emergency department (ED) visits for angioedema annually, and it ranks as the top allergic disorder resulting in hospitalization in the U.S.[32] ## See also[edit] * Drug-induced angioedema * Gleich's syndrome (unexplained angioedema with high eosinophil counts) * Ruconest (C1-inhibitor) ## References[edit] 1. ^ a b c d e f g h i j k l m n o p q r s t Bernstein, JA; Cremonesi, P; Hoffmann, TK; Hollingsworth, J (December 2017). "Angioedema in the emergency department: a practical guide to differential diagnosis and management". International Journal of Emergency Medicine. 10 (1): 15. doi:10.1186/s12245-017-0141-z. PMC 5389952. PMID 28405953. 2. ^ a b c Caterino, Jeffrey M.; Kahan, Scott (2003). In a Page: Emergency medicine. Lippincott Williams & Wilkins. p. 133. ISBN 9781405103572. Archived from the original on 2017-09-10. 3. ^ a b Habif, Thomas P. (2009). Clinical Dermatology E-Book (5 ed.). Elsevier Health Sciences. p. 182. ISBN 978-0323080378. Archived from the original on 2017-09-10. 4. ^ Bork K; Barnstedt Se (August 2003). "Laryngeal edema and death from asphyxiation after tooth extraction in four patients with hereditary angioedema". J Am Dent Assoc. 134 (8): 1088–94. doi:10.14219/jada.archive.2003.0323. PMID 12956349.[permanent dead link] 5. ^ Axelrod, S; Davis-Lorton, M (2011). "Urticaria and angioedema". The Mount Sinai Journal of Medicine, New York. 78 (5): 784–802. doi:10.1002/msj.20288. PMID 21913206. 6. ^ Moon, MD, Amanda T.; Heymann, MD, Warren R. "Acquired Angioedema". MedScape. Archived from the original on 5 September 2015. Retrieved 1 October 2015. 7. ^ Zuraw B.L. (September 2008). "Clinical practice. Hereditary angioedema". N. Engl. J. Med. 359 (10): 1027–36. doi:10.1056/NEJMcp0803977. PMID 18768946. 8. ^ Loew, Burr. "A 68-Year-Old Woman With Recurrent Abdominal Pain, Nausea, and Vomiting". MedScape. Archived from the original on 22 October 2012. Retrieved 19 October 2012. 9. ^ Bas M, Adams V, Suvorava T, Niehues T, Hoffmann TK, Kojda G (2007). "Nonallergic angioedema: role of bradykinin". Allergy. 62 (8): 842–56. doi:10.1111/j.1398-9995.2007.01427.x. PMID 17620062. S2CID 22772933. 10. ^ Bork K, Barnstedt SE, Koch P, Traupe H (2000). "Hereditary angioedema with normal C1-inhibitor activity in women". Lancet. 356 (9225): 213–7. doi:10.1016/S0140-6736(00)02483-1. PMID 10963200. S2CID 30105665. 11. ^ Cichon S, Martin L, Hennies HC, et al. (2006). "Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III". Am. J. Hum. Genet. 79 (6): 1098–104. doi:10.1086/509899. PMC 1698720. PMID 17186468. 12. ^ University of Maryland Medical Center. Angioedema. "Archived copy". Archived from the original on 2007-10-12. Retrieved 2008-01-08.CS1 maint: archived copy as title (link) 13. ^ a b Sabroe RA, Black AK (February 1997). "Angiotensin-converting enzyme (ACE) inhibitors and angio-oedema". British Journal of Dermatology. 136 (2): 153–8. doi:10.1111/j.1365-2133.1997.tb14887.x. PMID 9068723. 14. ^ a b Israili ZH, Hall WD (August 1, 1992). "Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology". Annals of Internal Medicine. 117 (3): 234–42. doi:10.7326/0003-4819-117-3-234. PMID 1616218. 15. ^ Kostis JB, Kim HJ, Rusnak J, Casale T, Kaplan A, Corren J, Levy E (July 25, 2005). "Incidence and characteristics of angioedema associated with enalapril". Archives of Internal Medicine. 165 (14): 1637–42. doi:10.1001/archinte.165.14.1637. PMID 16043683. 16. ^ Brown NJ, Ray WA, Snowden M, Griffin MR (July 1996). "Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema". Clinical Pharmacologic Therapy. 60 (1): 8–13. doi:10.1016/S0009-9236(96)90161-7. PMID 8689816. S2CID 12030323. 17. ^ Dykewicz, MS (August 2004). "Cough and angioedema from angiotensin-converting enzyme inhibitors: new insights into mechanisms and management". Current Opinion in Allergy and Clinical Immunology. 4 (4): 267–70. doi:10.1097/01.all.0000136759.43571.7f. PMID 15238791. S2CID 13313000. 18. ^ Malde B, Regalado J, Greenberger PA (January 2007). "Investigation of angioedema associated with the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers". Annals of Allergy, Asthma & Immunology. 98 (1): 57–63. doi:10.1016/S1081-1206(10)60860-5. PMID 17225721. 19. ^ Cicardi M, Zingale LC, Bergamaschini L, Agostoni A (April 26, 2004). "Angioedema associated with angiotensin-converting enzyme inhibitor use: outcome after switching to a different treatment". Archives of Internal Medicine. 164 (8): 910–3. doi:10.1001/archinte.164.8.910. PMID 15111379. 20. ^ LLC, Prime Therapeutics. "Study: Drug Costs for Rare Hereditary Angioedema Disorder Tripled in Two Years". www.prnewswire.com. Archived from the original on 2015-10-25. 21. ^ "Angioedema". Australasian Society of Clinical Immunology and Allergy (ASCIA). Retrieved 2020-03-24. 22. ^ "Archived copy" (PDF). Archived from the original (PDF) on 2007-09-28. Retrieved 2007-01-26.CS1 maint: archived copy as title (link) 23. ^ Drouet C, Désormeaux A, Robillard J, Ponard D, Bouillet L, Martin L, et al. (2008). "Metallopeptidase activities in hereditary angioedema: effect of androgen prophylaxis on plasma aminopeptidase P". The Journal of Allergy and Clinical Immunology. 121 (2): 429–33. doi:10.1016/j.jaci.2007.10.048. PMC 4126900. PMID 18158172. 24. ^ "FDA Approves Takhzyro (lanadelumab-flyo) for Hereditary Angioedema". Drugs.com. 25. ^ "FDA OKs New Prophylactic Drug for Rare Hereditary Angioedema". Medscape. 26. ^ Quincke H (1882). "Über akutes umschriebenes Hautödem". Monatsh Prakt Derm. 1: 129–131. 27. ^ synd/482 at Who Named It? 28. ^ Marcello Donati. De medica historia mirabili. Mantuae, per Fr. Osanam, 1586 29. ^ J. L. Milton. On giant urticaria. Edinburgh Medical Journal, 1876, 22: 513-526. 30. ^ Osler W (1888). "Hereditary angio-neurotic oedema". Am J Med Sci. 95 (2): 362–67. doi:10.1097/00000441-188804000-00004. S2CID 72808776. Reprint: PMID 20145434 31. ^ Donaldson VH, Evans RR (July 1963). "A biochemical abnormality in hereditary angioneurotic edema: absence of serum inhibitor of C' 1-esterase". Am. J. Med. 35: 37–44. doi:10.1016/0002-9343(63)90162-1. PMID 14046003. 32. ^ "Emergency Medicine, Allergy Physicians Partner to Create New Standards" (July 3, 2014). UC Academic Health Center. University of Cincinnati. http://healthnews.uc.edu/news/?/24791/ Archived 2014-07-14 at the Wayback Machine ## External links[edit] Classification D * ICD-10: D84.1, T78.3 * ICD-9-CM: 277.6, 995.1 * OMIM: 606860 106100 610618 * MeSH: D000799 * DiseasesDB: 13606 External resources * MedlinePlus: 000846 * eMedicine: emerg/32 med/135 ped/101 * Patient UK: Angioedema * Angioedema at Curlie * v * t * e Lymphoid and complement disorders causing immunodeficiency Primary Antibody/humoral (B) Hypogammaglobulinemia * X-linked agammaglobulinemia * Transient hypogammaglobulinemia of infancy Dysgammaglobulinemia * IgA deficiency * IgG deficiency * IgM deficiency * Hyper IgM syndrome (1 * 2 * 3 * 4 * 5) * Wiskott–Aldrich syndrome * Hyper-IgE syndrome Other * Common variable immunodeficiency * ICF syndrome T cell deficiency (T) * thymic hypoplasia: hypoparathyroid (Di George's syndrome) * euparathyroid (Nezelof syndrome * Ataxia–telangiectasia) peripheral: Purine nucleoside phosphorylase deficiency * Hyper IgM syndrome (1) Severe combined (B+T) * x-linked: X-SCID autosomal: Adenosine deaminase deficiency * Omenn syndrome * ZAP70 deficiency * Bare lymphocyte syndrome Acquired * HIV/AIDS Leukopenia: Lymphocytopenia * Idiopathic CD4+ lymphocytopenia Complement deficiency * C1-inhibitor (Angioedema/Hereditary angioedema) * Complement 2 deficiency/Complement 4 deficiency * MBL deficiency * Properdin deficiency * Complement 3 deficiency * Terminal complement pathway deficiency * Paroxysmal nocturnal hemoglobinuria * Complement receptor deficiency * v * t * e Consequences of external causes Temperature Elevated Hyperthermia Heat syncope Reduced Hypothermia Immersion foot syndromes Trench foot Tropical immersion foot Warm water immersion foot Chilblains Frostbite Aerosol burn Cold intolerance Acrocyanosis Erythrocyanosis crurum Radiation Radiation poisoning Radiation burn Chronic radiation keratosis Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy Radiation acne Radiation-induced cancer Radiation recall reaction Radiation-induced erythema multiforme Radiation-induced hypertrophic scar Radiation-induced keloid Radiation-induced morphea Air * Hypoxia/Asphyxia * Barotrauma * Aerosinusitis * Decompression sickness * High altitude * Altitude sickness * Chronic mountain sickness * Death zone * HAPE * HACE Food * Starvation Maltreatment * Physical abuse * Sexual abuse * Psychological abuse Travel * Motion sickness * Seasickness * Airsickness * Space adaptation syndrome Adverse effect * Hypersensitivity * Anaphylaxis * Angioedema * Allergy * Arthus reaction * Adverse drug reaction Other * Electrical injury * Drowning * Lightning injuries Ungrouped skin conditions resulting from physical factors * Dermatosis neglecta * Pinch mark * Pseudoverrucous papules and nodules * Sclerosing lymphangitis * Tropical anhidrotic asthenia * UV-sensitive syndrome environmental skin conditions Electrical burn frictional/traumatic/sports Black heel and palm Equestrian perniosis Jogger's nipple Pulling boat hands Runner's rump Surfer's knots Tennis toe Vibration white finger Weathering nodule of ear Wrestler's ear Coral cut Painful fat herniation Uranium dermatosis iv use Skin pop scar Skin track Slap mark Pseudoacanthosis nigricans Narcotic dermopathy * v * t * e Disorders of volume state Volume contraction * dehydration * hypovolemia Hypervolemia * Edema * Anasarca * Cerebral edema * Pulmonary edema * Angioedema * Lymphedema Other * Cause of fluid collection * Exudate * Transudate * By site * Hydrothorax * Ascites * Hydrosalpinx * Hyperemia [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Angioedema	c0002994	3,994	wikipedia	https://en.wikipedia.org/wiki/Angioedema	2021-01-18T18:34:00	{"mesh": ["D000799"], "umls": ["C0002994"], "wikidata": ["Q1129007"]}
For the plant genus, see Entomophobia (plant). Entomophobia is a specific phobia characterized by an excessive or unrealistic fear of one or more classes of insect, and classified as a phobia by the DSM-5.[1] More specific cases included apiphobia (fear of bees), myrmecophobia (fear of ants), and lepidopterophobia (fear of moths and butterflies). One book claims 6% of all US inhabitants have this phobia.[2] Entomophobia can be developed in some ways. One of them is by having a scary experience or if the person believes that the insect is dangerous. For example, if the person thinks a butterfly is venomous, they will do anything they can to avoid getting close to it. Entomophobia may develop after the person has had a traumatic experience with the insect(s) in question. It may develop early or later in life and is quite common among the animal phobias. Typically one has from a fear from one specific type of insect, and entomophobia leads to behavioral changes: the person with entomophobia will avoid situations where they may encounter the specific type of insect. Cognitive behavioral therapy is considered an effective treatment.[3] ## See also[edit] * Zoophobia * List of phobias ## References[edit] 1. ^ McCabe, Randi E. (2015). Milosevic, Irena; McCabe, Randi E. (eds.). Phobias: The Psychology of Irrational Fear: The Psychology of Irrational Fear. ABC-CLIO. pp. 125–27. ISBN 9781610695763. 2. ^ Lockwood, Jeffrey (2013-09-25). The Infested Mind: Why Humans Fear, Loathe, and Love Insects. Oxford UP. pp. 110–. ISBN 9780199374939. Retrieved 13 December 2015. 3. ^ McCabe, Randi E. (2015). Milosevic, Irena; McCabe, Randi E. (eds.). Phobias: The Psychology of Irrational Fear: The Psychology of Irrational Fear. ABC-CLIO. pp. 125–27. ISBN 9781610695763. * v * t * e Mental and behavioral disorders Adult personality and behavior Gender dysphoria * Ego-dystonic sexual orientation * Paraphilia * Fetishism * Voyeurism * Sexual maturation disorder * Sexual relationship disorder Other * Factitious disorder * Munchausen syndrome * Intermittent explosive disorder * Dermatillomania * Kleptomania * Pyromania * Trichotillomania * Personality disorder Childhood and learning Emotional and behavioral * ADHD * Conduct disorder * ODD * Emotional and behavioral disorders * Separation anxiety disorder * Movement disorders * Stereotypic * Social functioning * DAD * RAD * Selective mutism * Speech * Stuttering * Cluttering * Tic disorder * Tourette syndrome Intellectual disability * X-linked intellectual disability * Lujan–Fryns syndrome Psychological development (developmental disabilities) * Pervasive * Specific Mood (affective) * Bipolar * Bipolar I * Bipolar II * Bipolar NOS * Cyclothymia * Depression * Atypical depression * Dysthymia * Major depressive disorder * Melancholic depression * Seasonal affective disorder * Mania Neurological and symptomatic Autism spectrum * Autism * Asperger syndrome * High-functioning autism * PDD-NOS * Savant syndrome Dementia * AIDS dementia complex * Alzheimer's disease * Creutzfeldt–Jakob disease * Frontotemporal dementia * Huntington's disease * Mild cognitive impairment * Parkinson's disease * Pick's disease * Sundowning * Vascular dementia * Wandering Other * Delirium * Organic brain syndrome * Post-concussion syndrome Neurotic, stress-related and somatoform Adjustment * Adjustment disorder with depressed mood Anxiety Phobia * Agoraphobia * Social anxiety * Social phobia * Anthropophobia * Specific social phobia * Specific phobia * Claustrophobia Other * Generalized anxiety disorder * OCD * Panic attack * Panic disorder * Stress * Acute stress reaction * PTSD Dissociative * Depersonalization disorder * Dissociative identity disorder * Fugue state * Psychogenic amnesia Somatic symptom * Body dysmorphic disorder * Conversion disorder * Ganser syndrome * Globus pharyngis * Psychogenic non-epileptic seizures * False pregnancy * Hypochondriasis * Mass psychogenic illness * Nosophobia * Psychogenic pain * Somatization disorder Physiological and physical behavior Eating * Anorexia nervosa * Bulimia nervosa * Rumination syndrome * Other specified feeding or eating disorder Nonorganic sleep * Hypersomnia * Insomnia * Parasomnia * Night terror * Nightmare * REM sleep behavior disorder Postnatal * Postpartum depression * Postpartum psychosis Sexual dysfunction Arousal * Erectile dysfunction * Female sexual arousal disorder Desire * Hypersexuality * Hypoactive sexual desire disorder Orgasm * Anorgasmia * Delayed ejaculation * Premature ejaculation * Sexual anhedonia Pain * Nonorganic dyspareunia * Nonorganic vaginismus Psychoactive substances, substance abuse and substance-related * Drug overdose * Intoxication * Physical dependence * Rebound effect * Stimulant psychosis * Substance dependence * Withdrawal Schizophrenia, schizotypal and delusional Delusional * Delusional disorder * Folie à deux Psychosis and schizophrenia-like * Brief reactive psychosis * Schizoaffective disorder * Schizophreniform disorder Schizophrenia * Childhood schizophrenia * Disorganized (hebephrenic) schizophrenia * Paranoid schizophrenia * Pseudoneurotic schizophrenia * Simple-type schizophrenia Other * Catatonia Symptoms and uncategorized * Impulse control disorder * Klüver–Bucy syndrome * Psychomotor agitation * Stereotypy [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Entomophobia	None	3,995	wikipedia	https://en.wikipedia.org/wiki/Entomophobia	2021-01-18T18:34:24	{"wikidata": ["Q2157130"]}
A number sign (#) is used with this entry because primary sea-blue histiocytosis can be caused by mutation in the APOE gene (107741). Clinical Features This disorder is characterized by splenomegaly, mild thrombocytopenia, and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The name was coined by Silverstein et al. (1970). Holland et al. (1965) suggested that the syndrome is the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses. Jones et al. (1970) described an affected brother and sister. Parental consanguinity was possible because both parents came from the same restricted area of West Virginia. Lake et al. (1970) suggested that the 'sea-blue' designation be abandoned because the marrow contains a second variety of abnormal cell which never stains 'sea-blue' and because they had observed a 'malignant' disorder with 'sea-blue' cells and progressive neurologic disease characterized by ataxia, dementia, and seizures. Heterozygotes may have some sea-blue histiocytes in the bone marrow (Zlotnick and Fried, 1970). Wewalka (1970) gave a long-term follow-up on a case reported in 1950. He commented on eye changes: a white ring surrounding the macula. Berman (1972) described 2 sisters with this disorder in whom the initial diagnosis was Gaucher disease. The qualitative test for excessive mucopolysacchariduria was mildly positive in these patients. Sawitsky et al. (1972) added 2 families. In one, 4 brothers and a sister out of 7 sibs with normal parents were affected. The family was from Trinidad. In the second, an American black family, mother and daughter were affected. The authors concluded that this disorder is a lipidosis. They presented a pedigree of the family of Zlotnick and Fried (1970). The parents were first cousins in their Iranian Jewish family and showed changes consistent with carrier status. Sea-blue histiocytes have been observed in Norum disease (245900) (Jacobsen et al., 1972) and in Niemann-Pick disease type C1 (257220). Chainuvati et al. (1977) described the disease in a Thai brother and sister. The abnormal histiocytes were found in bone marrow and liver. Cirrhosis and absence of axillary hair were found in both. Blankenship et al. (1973) suggested the existence of a dominant variety, which they called the Lewis type for the name of the family. Three sibs had splenomegaly, peripheral neuropathy, cafe-au-lait spots and elevated serum acid phosphatase levels. The father, who was not known to be related to the mother, showed elevated bone marrow acid phosphatase and abnormal histiocytes. The Lewis type of Blankenship et al. (1973) subsequently was shown to be a form of Niemann-Pick disease (607616). The findings in the father represented, presumably, heterozygote manifestation. A presumably dominant but different form of sea-blue histiocyte disease was described by Swaiman et al. (1975), who found ceroid-lipofuscin storage and varied neurologic changes, especially posterior column degeneration, often beginning in the teens. Gait disturbance, positive Romberg and Babinski tests, and diminished vibratory and position senses were described. Zina and Bundino (1983) reported an affected brother and sister. The brother, aged 25 years, had skin lesions that contained sea-blue histiocytes. Like her brother, the sister, aged 17 years, had hepatosplenomegaly and pulmonary infiltrates; sea-blue histiocytes were demonstrated in muscles and subcutaneous tissue. Viana et al. (1990) reported sea-blue histiocytosis as a feature of 4 sibs in a Brazilian kindred with nonneuropathic (presumably type B) Niemann-Pick disease. Molecular Genetics Nguyen et al. (2000) described 2 unrelated probands with primary sea-blue histiocytosis who had normal or mildly elevated serum triglyceride concentrations that markedly increased after splenectomy. They provided evidence linking the syndrome to an inherited dominant APOE mutation (delta149 leu; 107741.0031) that causes a derangement in lipid metabolism and leads to splenomegaly in the absence of severe hypertriglyceridemia. In 2 brothers with splenomegaly, thrombocytopenia, and hypertriglyceridemia, Faivre et al. (2005) identified the delta149 leu mutation in the APOE gene. Their mother, who also had the mutation, had only isolated hypertriglyceridemia. One brother had a large beta band in the VLDL fraction and an elevated VLDL cholesterol-to-plasma triglyceride ratio; Faivre et al. (2005) suggested that the more severe phenotype might be explained by the presence of an APOE2 allele (107741.0001) in this patient. Eyes \- White ring surrounding the macula Inheritance \- Autosomal recessive \- ? same as the adult, chronic or B form of Niemann-Pick disease Lab \- Numerous bone marrow histiocytes with cytoplasmic granules which stain bright blue with the usual hematologic stains Heme \- Mild thrombocytopenia Hair \- Absent axillary hair GI \- Splenomegaly \- Cirrhosis ▲ 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	SEA-BLUE HISTIOCYTE DISEASE	c0036489	3,996	omim	https://www.omim.org/entry/269600	2019-09-22T16:22:29	{"doid": ["4423"], "mesh": ["D012618"], "omim": ["269600"], "orphanet": ["158029"], "synonyms": ["Alternative titles", "SEA-BLUE HISTIOCYTOSIS", "HISTIOCYTOSIS, SEA-BLUE"], "genereviews": ["NBK208534"]}
A number sign (#) is used with this entry because riboflavin deficiency is caused by heterozygous mutation in the SLC52A1 gene (607883) on chromosome 17p13. Clinical Features Chiong et al. (2007) reported a newborn who presented soon after birth with poor suck, hypoglycemia, and metabolic acidosis. She had dicarboxylic aciduria and elevated plasma acylcarnitine levels, initially thought to be consistent with multiple acyl-CoA dehydrogenase deficiency (MADD; 231680). Treatment with oral riboflavin resulted in complete resolution of the clinical and biochemical findings. Because of this rapid and compete response, maternal riboflavin deficiency was postulated and confirmed by serum testing. The mother reported severe vomiting and a restricted diet during pregnancy, but had no other signs or symptoms of riboflavin deficiency. While on a normal diet, the mother showed increased serum acylcarnitine levels, which normalized after riboflavin supplementation, suggesting that she had a primary deficiency in riboflavin metabolism. Riboflavin supplementation in the child was stopped at age 15 months, and she showed normal development. Primary MADD deficiency in the child was excluded by genetic analysis. The findings were consistent with transient neonatal riboflavin deficiency secondary to maternal riboflavin deficiency that was exacerbated during pregnancy. Ho et al. (2011) reported follow-up of the family reported by Chiong et al. (2007) and noted that the mother had a second unaffected child while taking oral riboflavin supplementation during pregnancy. Mosegaard et al. (2017) reported a female infant, conceived by in vitro fertility treatment with an anonymous sperm donor, with transient neonatal riboflavin deficiency. The patient's mother had experienced hyperemesis gravidarum and lost 20 kg during the pregnancy, but had no apparent signs or symptoms of riboflavin deficiency (sore mucous membranes, photophobia, or dermatitis). The infant presented at 4 days of age with lethargy, hypotonia, poor peripheral circulation, hypothermia, and metabolic lactic acidosis. Her acylcarnitine profile suggested a diagnosis of MADD. Following treatment with hemofiltration and riboflavin, repeat newborn screening analysis at 8 and 10 days of age showed acylcarnitines in the reference range and a nearly normal level of plasma acylcarnitines. Riboflavin levels in the mother's whole blood were at the lower limit of normal. Riboflavin levels could not be measured in the infant due to the transfusion. Riboflavin treatment was continued for 30 months, and carnitine substitution for 12 months. The child showed normal psychomotor development at age 3 years. Molecular Genetics In a woman with riboflavin deficiency who had an infant with transient neonatal riboflavin deficiency (Chiong et al., 2007), Ho et al. (2011) identified a de novo heterozygous 1.9-kb deletion in the SLC52A1 gene (607883.0001), predicted to result in haploinsufficiency. The infant did not carry the deletion. These findings confirmed that the transient clinical and metabolic abnormalities in the infant were the result of maternal riboflavin deficiency. In an infant with neonatal riboflavin deficiency, Mosegaard et al. (2017) identified heterozygosity for an intronic mutation in the SLC52A1 gene (607883.0002). The patient's unaffected mother was also heterozygous for the mutation. The father was not available for study. INHERITANCE \- Autosomal dominant LABORATORY ABNORMALITIES \- Increased plasma acylcarnitine levels (if untreated) MISCELLANEOUS \- One family has been reported (last curated January 2013) \- Mutation carrier is clinically asymptomatic \- Offspring of mutation carrier may show clinical signs of secondary riboflavin deficiency in the neonatal period \- Riboflavin supplementation normalizes any clinical or biochemical changes MOLECULAR BASIS \- Caused by mutation in the solute carrier family 52 (riboflavin transporter), member 1, gene (SLC52A1, 607883.0001 ) ▲ 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	RIBOFLAVIN DEFICIENCY	c0035528	3,997	omim	https://www.omim.org/entry/615026	2019-09-22T15:53:24	{"mesh": ["D012257"], "omim": ["615026"], "icd-9": ["266.0"], "icd-10": ["E53.0"], "orphanet": ["411712"], "synonyms": []}
Primary or exclusive sexual attraction to prepubescent children This article is about the sexual preference toward prepubescent children. It is not to be confused with hebephilia or ephebophilia. Pedophilia (alternatively spelt paedophilia) is a psychiatric disorder in which an adult or older adolescent experiences a primary or exclusive sexual attraction to prepubescent children.[1][2] Although girls typically begin the process of puberty at age 10 or 11, and boys at age 11 or 12,[3] criteria for pedophilia extend the cut-off point for prepubescence to age 13.[4] A person must be at least 16 years old, and at least five years older than the prepubescent child, for the attraction to be diagnosed as pedophilia.[4][5] Pedophilia is termed pedophilic disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and the manual defines it as a paraphilia involving intense and recurrent sexual urges towards and fantasies about prepubescent children that have either been acted upon or which cause the person with the attraction distress or interpersonal difficulty.[4] The International Classification of Diseases (ICD-11) defines it as a "sustained, focused, and intense pattern of sexual arousal—as manifested by persistent sexual thoughts, fantasies, urges, or behaviours—involving pre-pubertal children."[6] In popular usage, the word pedophilia is often applied to any sexual interest in children or the act of child sexual abuse.[1][2][7] This use conflates the sexual attraction to prepubescent children with the act of child sexual abuse and fails to distinguish between attraction to prepubescent and pubescent or post-pubescent minors.[8][9] Researchers recommend that these imprecise uses be avoided, because although some people who commit child sexual abuse are pedophiles,[7][10] child sexual abuse offenders are not pedophiles unless they have a primary or exclusive sexual interest in prepubescent children,[8][11][12] and some pedophiles do not molest children.[13] Pedophilia was first formally recognized and named in the late 19th century. A significant amount of research in the area has taken place since the 1980s. Although mostly documented in men, there are also women who exhibit the disorder,[14][15] and researchers assume available estimates underrepresent the true number of female pedophiles.[16] No cure for pedophilia has been developed, but there are therapies that can reduce the incidence of a person committing child sexual abuse.[7] The exact causes of pedophilia have not been conclusively established.[17] Some studies of pedophilia in child sex offenders have correlated it with various neurological abnormalities and psychological pathologies.[18] In the United States, following Kansas v. Hendricks in 1997, sex offenders who are diagnosed with certain mental disorders, particularly pedophilia, can be subject to indefinite involuntary commitment.[19] ## Contents * 1 Definitions * 2 Signs and symptoms * 2.1 Development * 2.2 Comorbidity and personality traits * 2.3 Child pornography * 3 Causes * 4 Diagnosis * 4.1 DSM and ICD-11 * 4.2 Debate regarding criteria * 5 Treatment * 5.1 General * 5.2 Cognitive behavioral therapy * 5.3 Behavioral interventions * 5.4 Sex drive reduction * 6 Epidemiology * 6.1 Pedophilia and child molestation * 7 History * 8 Law and forensic psychology * 8.1 Definitions * 8.2 Civil and legal commitment * 9 Society and culture * 9.1 General * 9.2 Misuse of medical terminology * 9.3 Pedophile advocacy groups * 9.4 Anti-pedophile activism * 10 See also * 11 References * 12 Further reading * 13 External links ## Definitions The word pedophilia comes from the Greek παῖς, παιδός (paîs, paidós), meaning "child", and φιλία (philía), "friendly love" or "friendship".[20] Pedophilia is used for individuals with a primary or exclusive sexual interest in prepubescent children aged 13 or younger.[4][5] Infantophilia is a sub-type of pedophilia; it is used to refer to a sexual preference for children under the age of 5 (especially infants and toddlers).[21][10] This is sometimes referred to as nepiophilia (from the Greek: νήπιος (népios) meaning "infant" or "child," which in turn derives from "ne-" and "epos" meaning "not speaking"), though this term is rarely used in academic sources.[22][23] Hebephilia is defined as individuals with a primary or exclusive sexual interest in 11- to 14-year-old pubescents.[24] The DSM-5 does not list hebephilia among the diagnoses; while evidence suggests that hebephilia is separate from pedophilia, the ICD-10 includes early pubertal age (an aspect of hebephilia) in its pedophilia definition, covering the physical development overlap between the two philias.[25] In addition to hebephilia, some clinicians have proposed other categories that are somewhat or completely distinguished from pedophilia; these include pedohebephilia (a combination of pedophilia and hebephilia) and ephebophilia (though ephebophilia is not considered pathological).[26][27] ## Signs and symptoms ### Development Pedophilia emerges before or during puberty, and is stable over time.[28] It is self-discovered, not chosen.[7] For these reasons, pedophilia has been described as a disorder of sexual preference, phenomenologically similar to a heterosexual or homosexual orientation.[28] These observations, however, do not exclude pedophilia from the group of mental disorders because pedophilic acts cause harm, and mental health professionals can sometimes help pedophiles to refrain from harming children.[29] In response to misinterpretations that the American Psychiatric Association considers pedophilia a sexual orientation because of wording in its printed DSM-5 manual, which distinguishes between paraphilia and what it calls "paraphilic disorder", subsequently forming a division of "pedophilia" and "pedophilic disorder", the association commented: "'[S]exual orientation' is not a term used in the diagnostic criteria for pedophilic disorder and its use in the DSM-5 text discussion is an error and should read 'sexual interest.'" They added, "In fact, APA considers pedophilic disorder a 'paraphilia,' not a 'sexual orientation.' This error will be corrected in the electronic version of DSM-5 and the next printing of the manual." They said they strongly support efforts to criminally prosecute those who sexually abuse and exploit children and adolescents, and "also support continued efforts to develop treatments for those with pedophilic disorder with the goal of preventing future acts of abuse."[30] ### Comorbidity and personality traits Studies of pedophilia in child sex offenders often report that it co-occurs with other psychopathologies, such as low self-esteem,[31] depression, anxiety, and personality problems. It is not clear whether these are features of the disorder itself, artifacts of sampling bias, or consequences of being identified as a sex offender.[18] One review of the literature concluded that research on personality correlates and psychopathology in pedophiles is rarely methodologically correct, in part owing to confusion between pedophiles and child sex offenders, as well as the difficulty of obtaining a representative, community sample of pedophiles.[32] Seto (2004) points out that pedophiles who are available from a clinical setting are likely there because of distress over their sexual preference or pressure from others. This increases the likelihood that they will show psychological problems. Similarly, pedophiles recruited from a correctional setting have been convicted of a crime, making it more likely that they will show anti-social characteristics.[33] Impaired self-concept and interpersonal functioning were reported in a sample of child sex offenders who met the diagnostic criteria for pedophilia by Cohen et al. (2002), which the authors suggested could contribute to motivation for pedophilic acts. The pedophilic offenders in the study had elevated psychopathy and cognitive distortions compared to healthy community controls. This was interpreted as underlying their failure to inhibit their criminal behavior.[34] Studies in 2009 and 2012 found that non-pedophilic child sex offenders exhibited psychopathy, but pedophiles did not.[35][36] Wilson and Cox (1983) studied the characteristics of a group of pedophile club members. The most marked differences between pedophiles and controls were on the introversion scale, with pedophiles showing elevated shyness, sensitivity and depression. The pedophiles scored higher on neuroticism and psychoticism, but not enough to be considered pathological as a group. The authors caution that "there is a difficulty in untangling cause and effect. We cannot tell whether paedophiles gravitate towards children because, being highly introverted, they find the company of children less threatening than that of adults, or whether the social withdrawal implied by their introversion is a result of the isolation engendered by their preference i.e., awareness of the social [dis]approbation and hostility that it evokes" (p. 324).[37] In a non-clinical survey, 46% of pedophiles reported that they had seriously considered suicide for reasons related to their sexual interest, 32% planned to carry it out, and 13% had already attempted it.[38] A review of qualitative research studies published between 1982 and 2001 concluded that child sexual abusers use cognitive distortions to meet personal needs, justifying abuse by making excuses, redefining their actions as love and mutuality, and exploiting the power imbalance inherent in all adult–child relationships.[39] Other cognitive distortions include the idea of "children as sexual beings", uncontrollability of sexual behavior, and "sexual entitlement-bias".[40] ### Child pornography Consumption of child pornography is a more reliable indicator of pedophilia than molesting a child,[41] although some non-pedophiles also view child pornography.[42] Child pornography may be used for a variety of purposes, ranging from private sexual gratification or trading with other collectors, to preparing children for sexual abuse as part of the child grooming process.[43][44][45] Pedophilic viewers of child pornography are often obsessive about collecting, organizing, categorizing, and labeling their child pornography collection according to age, gender, sex act and fantasy.[46] According to FBI agent Ken Lanning, "collecting" pornography does not mean that they merely view pornography, but that they save it, and "it comes to define, fuel, and validate their most cherished sexual fantasies".[42] Lanning states that the collection is the single best indicator of what the offender wants to do, but not necessarily of what has been or will be done.[47] Researchers Taylor and Quayle reported that pedophilic collectors of child pornography are often involved in anonymous internet communities dedicated to extending their collections.[48] ## Causes Although what causes pedophilia is not yet known, researchers began reporting a series of findings linking pedophilia with brain structure and function, beginning in 2002. Testing individuals from a variety of referral sources inside and outside the criminal justice system as well as controls, these studies found associations between pedophilia and lower IQs,[49][50][51] poorer scores on memory tests,[50] greater rates of non-right-handedness,[49][50][52][53] greater rates of school grade failure over and above the IQ differences,[54] lesser physical height,[55][56] greater probability of having suffered childhood head injuries resulting in unconsciousness,[57][58] and several differences in MRI-detected brain structures.[59][60][61] Such studies suggest that there are one or more neurological characteristics present at birth that cause or increase the likelihood of being pedophilic. Some studies have found that pedophiles are less cognitively impaired than non-pedophilic child molesters.[62] A 2011 study reported that pedophilic child molesters had deficits in response inhibition, but no deficits in memory or cognitive flexibility.[63] Evidence of familial transmittability "suggests, but does not prove that genetic factors are responsible" for the development of pedophilia.[64] A 2015 study indicated that pedophilic offenders have a normal IQ.[65] Another study, using structural MRI, indicated that male pedophiles have a lower volume of white matter than a control group.[59] Functional magnetic resonance imaging (fMRI) has indicated that child molesters diagnosed with pedophilia have reduced activation of the hypothalamus as compared with non-pedophilic persons when viewing sexually arousing pictures of adults.[66] A 2008 functional neuroimaging study notes that central processing of sexual stimuli in heterosexual "paedophile forensic inpatients" may be altered by a disturbance in the prefrontal networks, which "may be associated with stimulus-controlled behaviours, such as sexual compulsive behaviours". The findings may also suggest "a dysfunction at the cognitive stage of sexual arousal processing".[67] Blanchard, Cantor, and Robichaud (2006) reviewed the research that attempted to identify hormonal aspects of pedophiles.[68] They concluded that there is some evidence that pedophilic men have less testosterone than controls, but that the research is of poor quality and that it is difficult to draw any firm conclusion from it. While not causes of pedophilia themselves, childhood abuse by adults or comorbid psychiatric illnesses—such as personality disorders and substance abuse—are risk factors for acting on pedophilic urges.[7] Blanchard, Cantor, and Robichaud addressed comorbid psychiatric illnesses that, "The theoretical implications are not so clear. Do particular genes or noxious factors in the prenatal environment predispose a male to develop both affective disorders and pedophilia, or do the frustration, danger, and isolation engendered by unacceptable sexual desires—or their occasional furtive satisfaction—lead to anxiety and despair?"[68] They indicated that, because they previously found mothers of pedophiles to be more likely to have undergone psychiatric treatment, the genetic possibility is more likely.[57] A study analyzing the sexual fantasies of 200 heterosexual men by using the Wilson Sex Fantasy Questionnaire exam determined that males with a pronounced degree of paraphilic interest (including pedophilia) had a greater number of older brothers, a high 2D:4D digit ratio (which would indicate low prenatal androgen exposure), and an elevated probability of being left-handed, suggesting that disturbed hemispheric brain lateralization may play a role in deviant attractions.[69] ## Diagnosis ### DSM and ICD-11 The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) has a significantly larger diagnostic features section for pedophilia than the previous DSM version, the DSM-IV-TR, and states, "The diagnostic criteria for pedophilic disorder are intended to apply both to individuals who freely disclose this paraphilia and to individuals who deny any sexual attraction to prepubertal children (generally age 13 years or younger), despite substantial objective evidence to the contrary."[4] Like the DSM-IV-TR, the manual outlines specific criteria for use in the diagnosis of this disorder. These include the presence of sexually arousing fantasies, behaviors or urges that involve some kind of sexual activity with a prepubescent child (with the diagnostic criteria for the disorder extending the cut-off point for prepubescence to age 13) for six months or more, or that the subject has acted on these urges or suffers from distress as a result of having these feelings. The criteria also indicate that the subject should be 16 or older and that the child or children they fantasize about are at least five years younger than them, though ongoing sexual relationships between a 12- to 13-year-old and a late adolescent are advised to be excluded. A diagnosis is further specified by the sex of the children the person is attracted to, if the impulses or acts are limited to incest, and if the attraction is "exclusive" or "nonexclusive".[4] The ICD-10 defines pedophilia as "a sexual preference for children, boys or girls or both, usually of prepubertal or early pubertal age".[70] Like the DSM, this system's criteria require that the person be at least 16 years of age or older before being diagnosed as a pedophile. The person must also have a persistent or predominant sexual preference for prepubescent children at least five years younger than them.[5] The ICD-11 defines pedophilic disorder as a "sustained, focused, and intense pattern of sexual arousal—as manifested by persistent sexual thoughts, fantasies, urges, or behaviours—involving pre-pubertal children."[6] It also states that for a diagnosis of pedophilic disorder, "the individual must have acted on these thoughts, fantasies or urges or be markedly distressed by them. This diagnosis does not apply to sexual behaviours among pre- or post-pubertal children with peers who are close in age."[6] Several terms have been used to distinguish "true pedophiles" from non-pedophilic and non-exclusive offenders, or to distinguish among types of offenders on a continuum according to strength and exclusivity of pedophilic interest, and motivation for the offense (see child sexual offender types). Exclusive pedophiles are sometimes referred to as true pedophiles. They are sexually attracted to prepubescent children, and only prepubescent children. Showing no erotic interest in adults, they can only become sexually aroused while fantasizing about or being in the presence of prepubescent children, or both.[16] Non-exclusive offenders—or "non-exclusive pedophiles"—may at times be referred to as non-pedophilic offenders, but the two terms are not always synonymous. Non-exclusive offenders are sexually attracted to both children and adults, and can be sexually aroused by both, though a sexual preference for one over the other in this case may also exist. If the attraction is a sexual preference for prepubescent children, such offenders are considered pedophiles in the same vein as exclusive offenders.[70][16] Neither the DSM nor the ICD-11 diagnostic criteria require actual sexual activity with a prepubescent youth. The diagnosis can therefore be made based on the presence of fantasies or sexual urges even if they have never been acted upon. On the other hand, a person who acts upon these urges yet experiences no distress about their fantasies or urges can also qualify for the diagnosis. Acting on sexual urges is not limited to overt sex acts for purposes of this diagnosis, and can sometimes include indecent exposure, voyeuristic or frotteuristic behaviors,[4] or masturbating to child pornography.[41] Often, these behaviors need to be considered in-context with an element of clinical judgment before a diagnosis is made. Likewise, when the patient is in late adolescence, the age difference is not specified in hard numbers and instead requires careful consideration of the situation.[71] Ego-dystonic sexual orientation (F66.1) includes people who acknowledge that they have a sexual preference for prepubertal children, but wish to change it due to the associated psychological or behavioral problems (or both). ### Debate regarding criteria There was discussion on the DSM-IV-TR being overinclusive and underinclusive. Its criterion A concerns sexual fantasies or sexual urges regarding prepubescent children, and its criterion B concerns acting on those urges or the urges causing marked distress or interpersonal difficulty. Several researchers discussed whether or not a "contented pedophile"—an individual who fantasizes about having sex with a child and masturbates to these fantasies, but does not commit child sexual abuse, and who does not feel subjectively distressed afterward—met the DSM-IV-TR criteria for pedophilia since this person did not meet criterion B.[25][72][73][74] Criticism also concerned someone who met criterion B, but did not meet criterion A. A large-scale survey about usage of different classification systems showed that the DSM classification is only rarely used. As an explanation, it was suggested that the underinclusiveness, as well as a lack of validity, reliability and clarity might have led to the rejection of the DSM classification.[75] Ray Blanchard, an American-Canadian sexologist known for his research studies on pedophilia, addressed (in his literature review for the DSM-5) the objections to the overinclusiveness and under underinclusiveness of the DSM-IV-TR, and proposed a general solution applicable to all paraphilias. This meant namely a distinction between paraphilia and paraphilic disorder. The latter term is proposed to identify the diagnosable mental disorder which meets Criterion A and B, whereas an individual who does not meet Criterion B can be ascertained but not diagnosed as having a paraphilia.[76] Blanchard and a number of his colleagues also proposed that hebephilia become a diagnosable mental disorder under the DSM-5 to resolve the physical development overlap between pedophilia and hebephilia by combining the categories under pedophilic disorder, but with specifiers on which age range (or both) is the primary interest.[26][77] The proposal for hebephilia was rejected by the American Psychiatric Association,[78] but the distinction between paraphilia and paraphilic disorder was implemented.[4][79] The American Psychiatric Association stated that "[i]n the case of pedophilic disorder, the notable detail is what wasn't revised in the new manual. Although proposals were discussed throughout the DSM-5 development process, diagnostic criteria ultimately remained the same as in DSM-IV TR" and that "[o]nly the disorder name will be changed from pedophilia to pedophilic disorder to maintain consistency with the chapter’s other listings."[79] If hebephilia had been accepted as a DSM-5 diagnosable disorder, it would have been similar to the ICD-10 definition of pedophilia that already includes early pubescents,[25] and would have raised the minimum age required for a person to be able to be diagnosed with pedophilia from 16 years to 18 years (with the individual needing to be at least 5 years older than the minor).[26] O'Donohue, however, suggests that the diagnostic criteria for pedophilia be simplified to the attraction to children alone if ascertained by self-report, laboratory findings, or past behavior. He states that any sexual attraction to children is pathological and that distress is irrelevant, noting "this sexual attraction has the potential to cause significant harm to others and is also not in the best interests of the individual."[80] Also arguing for behavioral criteria in defining pedophilia, Howard E. Barbaree and Michael C. Seto disagreed with the American Psychiatric Association's approach in 1997 and instead recommended the use of actions as the sole criterion for the diagnosis of pedophilia, as a means of taxonomic simplification.[81] ## Treatment ### General There is no evidence that pedophilia can be cured.[25] Instead, most therapies focus on helping the pedophile refrain from acting on their desires.[7][82] Some therapies do attempt to cure pedophilia, but there are no studies showing that they result in a long-term change in sexual preference.[83] Michael Seto suggests that attempts to cure pedophilia in adulthood are unlikely to succeed because its development is influenced by prenatal factors.[25] Pedophilia appears to be difficult to alter but pedophiles can be helped to control their behavior, and future research could develop a method of prevention.[84] There are several common limitations to studies of treatment effectiveness. Most categorize their participants by behavior rather than erotic age preference, which makes it difficult to know the specific treatment outcome for pedophiles.[7] Many do not select their treatment and control groups randomly. Offenders who refuse or quit treatment are at higher risk of offending, so excluding them from the treated group, while not excluding those who would have refused or quit from the control group, can bias the treated group in favor of those with lower recidivism.[25][85] The effectiveness of treatment for non-offending pedophiles has not been studied.[25] ### Cognitive behavioral therapy Cognitive behavioral therapy (CBT) aims to reduce attitudes, beliefs, and behaviors that may increase the likelihood of sexual offenses against children. Its content varies widely between therapists, but a typical program might involve training in self-control, social competence and empathy, and use cognitive restructuring to change views on sex with children. The most common form of this therapy is relapse prevention, where the patient is taught to identify and respond to potentially risky situations based on principles used for treating addictions.[86] The evidence for cognitive behavioral therapy is mixed.[86] A 2012 Cochrane Review of randomized trials found that CBT had no effect on risk of reoffending for contact sex offenders.[87] Meta-analyses in 2002 and 2005, which included both randomized and non-randomized studies, concluded that CBT reduced recidivism.[88][89] There is debate over whether non-randomized studies should be considered informative.[25][90] More research is needed.[87] ### Behavioral interventions Behavioral treatments target sexual arousal to children, using satiation and aversion techniques to suppress sexual arousal to children and covert sensitization (or masturbatory reconditioning) to increase sexual arousal to adults.[91] Behavioral treatments appear to have an effect on sexual arousal patterns during phallometric testing, but it is not known whether the effect represents changes in sexual interests or changes in the ability to control genital arousal during testing, nor whether the effect persists in the long term.[92][93] For sex offenders with mental disabilities, applied behavior analysis has been used.[94] ### Sex drive reduction Pharmacological interventions are used to lower the sex drive in general, which can ease the management of pedophilic feelings, but does not change sexual preference.[95] Antiandrogens work by interfering with the activity of testosterone. Cyproterone acetate (Androcur) and medroxyprogesterone acetate (Depo-Provera) are the most commonly used. The efficacy of antiantrogens has some support, but few high-quality studies exist. Cyproterone acetate has the strongest evidence for reducing sexual arousal, while findings on medroxyprogesterone acetate have been mixed.[96] Gonadotropin-releasing hormone analogues such as leuprorelin (Lupron), which last longer and have fewer side-effects, are also used to reduce libido,[97] as are selective serotonin reuptake inhibitors.[96] The evidence for these alternatives is more limited and mostly based on open trials and case studies.[25] All of these treatments, commonly referred to as "chemical castration", are often used in conjunction with cognitive behavioral therapy.[98] According to the Association for the Treatment of Sexual Abusers, when treating child molesters, "anti-androgen treatment should be coupled with appropriate monitoring and counseling within a comprehensive treatment plan."[99] These drugs may have side-effects, such as weight gain, breast development, liver damage and osteoporosis.[25] Historically, surgical castration was used to lower sex drive by reducing testosterone. The emergence of pharmacological methods of adjusting testosterone has made it largely obsolete, because they are similarly effective and less invasive.[95] It is still occasionally performed in Germany, the Czech Republic, Switzerland, and a few U.S. states. Non-randomized studies have reported that surgical castration reduces recidivism in contact sex offenders.[100] The Association for the Treatment of Sexual Abusers opposes surgical castration[99] and the Council of Europe works to bring the practice to an end in Eastern European countries where it is still applied through the courts.[101] ## Epidemiology ### Pedophilia and child molestation The prevalence of pedophilia in the general population is not known,[25][33] but is estimated to be lower than 5% among adult men.[25] Less is known about the prevalence of pedophilia in women, but there are case reports of women with strong sexual fantasies and urges towards children.[14] Most sexual offenders against children are male. Females may account for 0.4% to 4% of convicted sexual offenders, and one study estimates a 10 to 1 ratio of male-to-female child molesters.[16] The true number of female child molesters may be underrepresented by available estimates, for reasons including a "societal tendency to dismiss the negative impact of sexual relationships between young boys and adult women, as well as women's greater access to very young children who cannot report their abuse", among other explanations.[16] The term pedophile is commonly used by the public to describe all child sexual abuse offenders.[8][12] This usage is considered problematic by researchers, because many child molesters do not have a strong sexual interest in prepubescent children, and are consequently not pedophiles.[11][12][25] There are motives for child sexual abuse that are unrelated to pedophilia,[81] such as stress, marital problems, the unavailability of an adult partner,[102] general anti-social tendencies, high sex drive or alcohol use.[103] As child sexual abuse is not automatically an indicator that its perpetrator is a pedophile, offenders can be separated into two types: pedophilic and non-pedophilic[104] (or preferential and situational).[9] Estimates for the rate of pedophilia in detected child molesters generally range between 25% and 50%.[105] A 2006 study found that 35% of its sample of child molesters were pedophilic.[106] Pedophilia appears to be less common in incest offenders,[107] especially fathers and step-fathers.[108] According to a U.S. study on 2429 adult male sex offenders who were categorized as "pedophiles", only 7% identified themselves as exclusive; indicating that many or most child sexual abusers may fall into the non-exclusive category.[10] Some pedophiles do not molest children.[2] Little is known about this population because most studies of pedophilia use criminal or clinical samples, which may not be representative of pedophiles in general.[109] Researcher Michael Seto suggests that pedophiles who commit child sexual abuse do so because of other anti-social traits in addition to their sexual attraction. He states that pedophiles who are "reflective, sensitive to the feelings of others, averse to risk, abstain from alcohol or drug use, and endorse attitudes and beliefs supportive of norms and the laws" may be unlikely to abuse children.[25] A 2015 study indicates that pedophiles who molested children are neurologically distinct from non-offending pedophiles. The pedophilic molesters had neurological deficits suggestive of disruptions in inhibitory regions of the brain, while non-offending pedophiles had no such deficits.[110] According to Abel, Mittleman, and Becker[111] (1985) and Ward et al. (1995), there are generally large distinctions between the characteristics of pedophilic and non-pedophilic molesters. They state that non-pedophilic offenders tend to offend at times of stress; have a later onset of offending; and have fewer, often familial, victims, while pedophilic offenders often start offending at an early age; often have a larger number of victims who are frequently extrafamilial; are more inwardly driven to offend; and have values or beliefs that strongly support an offense lifestyle. One study found that pedophilic molesters had a median of 1.3 victims for those with girl victims and 4.4 for those with boy victims.[105] Child molesters, pedophilic or not, employ a variety of methods to gain sexual access to children. Some groom their victims into compliance with attention and gifts, while others use threats, alcohol or drugs, or physical force.[112] ## History Pedophilia is believed to have occurred in humans throughout history,[113] but was not formally named, defined or studied until the late 19th century. The term paedophilia erotica was coined in an 1886 article by the Viennese psychiatrist Richard von Krafft-Ebing but does not enter the author's Psychopathia Sexualis[114] until the 10th German edition.[115] A number of authors anticipated Krafft-Ebing's diagnostic gesture.[115] In Psychopathia Sexualis, the term appears in a section titled "Violation of Individuals Under the Age of Fourteen", which focuses on the forensic psychiatry aspect of child sexual offenders in general. Krafft-Ebing describes several typologies of offender, dividing them into psychopathological and non-psychopathological origins, and hypothesizes several apparent causal factors that may lead to the sexual abuse of children.[114] Krafft-Ebing mentioned paedophilia erotica in a typology of "psycho-sexual perversion". He wrote that he had only encountered it four times in his career and gave brief descriptions of each case, listing three common traits: 1. The individual is tainted [by heredity] (hereditär belastete)[116] 2. The subject's primary attraction is to children, rather than adults. 3. The acts committed by the subject are typically not intercourse, but rather involve inappropriate touching or manipulating the child into performing an act on the subject. He mentions several cases of pedophilia among adult women (provided by another physician), and also considered the abuse of boys by homosexual men to be extremely rare.[114] Further clarifying this point, he indicated that cases of adult men who have some medical or neurological disorder and abuse a male child are not true pedophilia and that, in his observation, victims of such men tended to be older and pubescent. He also lists pseudopaedophilia as a related condition wherein "individuals who have lost libido for the adult through masturbation and subsequently turn to children for the gratification of their sexual appetite" and claimed this is much more common.[114] Austrian neurologist Sigmund Freud briefly wrote about the topic in his 1905 book Three Essays on the Theory of Sexuality in a section titled The Sexually immature and Animals as Sexual objects. He wrote that exclusive pedophilia was rare and only occasionally were prepubescent children exclusive objects. He wrote that they usually were the subject of desire when a weak person "makes use of such substitutes" or when an uncontrollable instinct which will not allow delay seeks immediate gratification and cannot find a more appropriate object.[117] In 1908, Swiss neuroanatomist and psychiatrist Auguste Forel wrote of the phenomenon, proposing that it be referred to it as "Pederosis", the "Sexual Appetite for Children". Similar to Krafft-Ebing's work, Forel made the distinction between incidental sexual abuse by persons with dementia and other organic brain conditions, and the truly preferential and sometimes exclusive sexual desire for children. However, he disagreed with Krafft-Ebing in that he felt the condition of the latter was largely ingrained and unchangeable.[118] The term pedophilia became the generally accepted term for the condition and saw widespread adoption in the early 20th century, appearing in many popular medical dictionaries such as the 5th Edition of Stedman's in 1918. In 1952, it was included in the first edition of the Diagnostic and Statistical Manual of Mental Disorders.[119] This edition and the subsequent DSM-II listed the disorder as one subtype of the classification "Sexual Deviation", but no diagnostic criteria were provided. The DSM-III, published in 1980, contained a full description of the disorder and provided a set of guidelines for diagnosis.[120] The revision in 1987, the DSM-III-R, kept the description largely the same, but updated and expanded the diagnostic criteria.[121] ## Law and forensic psychology ### Definitions Pedophilia is not a legal term,[10] and having a sexual attraction to children is not illegal.[7] In law enforcement circles, the term pedophile is sometimes used informally to refer to any person who commits one or more sexually-based crimes that relate to legally underage victims. These crimes may include child sexual abuse, statutory rape, offenses involving child pornography, child grooming, stalking, and indecent exposure. One unit of the United Kingdom's Child Abuse Investigation Command is known as the "Paedophile Unit" and specializes in online investigations and enforcement work.[122] Some forensic science texts, such as Holmes (2008), use the term to refer to offenders who target child victims, even when such children are not the primary sexual interest of the offender.[123] FBI agent Kenneth Lanning, however, makes a point of distinguishing between pedophiles and child molesters.[124] ### Civil and legal commitment In the United States, following Kansas v. Hendricks, sex offenders who have certain mental disorders, including pedophilia, can be subject to indefinite civil commitment under various state laws[19] (generically called SVP laws[125]) and the federal Adam Walsh Child Protection and Safety Act of 2006.[126] Similar legislation exists in Canada.[19] In Kansas v. Hendricks, the US Supreme Court upheld as constitutional a Kansas law, the Sexually Violent Predator Act, under which Hendricks, a pedophile, was found to have a "mental abnormality" defined as a "congenital or acquired condition affecting the emotional or volitional capacity which predisposes the person to commit sexually violent offenses to the degree that such person is a menace to the health and safety of others", which allowed the State to confine Hendricks indefinitely irrespective of whether the State provided any treatment to him.[127][128][129] In United States v. Comstock, this type of indefinite confinement was upheld for someone previously convicted on child pornography charges; this time a federal law was involved—the Adam Walsh Child Protection and Safety Act.[126][130] The Walsh Act does not require a conviction on a sex offense charge, but only that the person be a federal prisoner, and one who "has engaged or attempted to engage in sexually violent conduct or child molestation and who is sexually dangerous to others", and who "would have serious difficulty in refraining from sexually violent conduct or child molestation if released".[131] In the US, offenders with pedophilia are more likely to be recommended for civil commitment than non-pedophilic offenders. About half of committed offenders have a diagnosis of pedophilia.[19] Psychiatrist Michael First writes that, since not all people with a paraphilia have difficulty controlling their behavior, the evaluating clinician must present additional evidence of volitional impairment instead of recommending commitment based on pedophilia alone.[132] ## Society and culture ### General Pedophilia is one of the most stigmatized mental disorders.[38] One study reported high levels of anger, fear and social rejection towards pedophiles who have not committed a crime.[133] The authors suggested such attitudes could negatively impact child sexual abuse prevention by reducing pedophiles' mental stability and discouraging them from seeking help.[38] According to sociologists Melanie-Angela Neuilly and Kristen Zgoba, social concern over pedophilia intensified greatly in the 1990s, coinciding with several sensational sex crimes (but a general decline in child sexual abuse rates). They found that the word pedophile appeared only rarely in The New York Times and Le Monde before 1996, with zero mentions in 1991.[134] Social attitudes towards child sexual abuse are extremely negative, with some surveys ranking it as morally worse than murder.[135] Early research showed that there was a great deal of misunderstanding and unrealistic perceptions in the general public about child sexual abuse and pedophiles. However, a 2004 study concluded that the public was well-informed on some aspects of these subjects.[136] ### Misuse of medical terminology The words pedophile and pedophilia are commonly used informally to describe an adult's sexual interest in pubescent or post-pubescent teenagers. The terms hebephilia or ephebophilia may be more accurate in these cases.[10][27][137] Another common usage of pedophilia is to refer to the act of sexual abuse itself,[2] rather than the medical meaning, which is a preference for prepubescents on the part of the older individual (see above for an explanation of the distinction).[8][9] There are also situations where the terms are misused to refer to relationships where the younger person is an adult of legal age, but is either considered too young in comparison to their older partner, or the older partner occupies a position of authority over them.[138] Researchers state that the above uses of the term pedophilia are imprecise or suggest that they are best avoided.[8][27] The Mayo Clinic states that pedophilia "is not a criminal or legal term".[10] ### Pedophile advocacy groups See also: Category:Pedophile advocacy and List of pedophile advocacy organizations From the late 1950s to early 1990s, several pedophile membership organizations advocated age of consent reform to lower or abolish age of consent laws,[139][140][141] as well as for the acceptance of pedophilia as a sexual orientation rather than a psychological disorder,[142] and for the legalization of child pornography.[141] The efforts of pedophile advocacy groups did not gain mainstream acceptance,[139][141][143][144][145] and today those few groups that have not dissolved have only minimal membership and have ceased their activities other than through a few websites.[141][145][146][147] In contrast to these organizations, members of the support group Virtuous Pedophiles believe that child sexual abuse is wrong and seek to raise awareness that some pedophiles do not offend;[148][149] this is generally not considered pedophile advocacy, as the Virtuous Pedophiles organization does not approve of the legalization of child pornography and does not support age of consent reform.[150] ### Anti-pedophile activism Main article: Anti-pedophile activism Anti-pedophile activism encompasses opposition against pedophiles, against pedophile advocacy groups, and against other phenomena that are seen as related to pedophilia, such as child pornography and child sexual abuse.[151] Much of the direct action classified as anti-pedophile involves demonstrations against sex offenders, against pedophiles advocating for the legalization of sexual activity between adults and children, and against Internet users who solicit sex from minors.[152][153][154][155] High-profile media attention to pedophilia has led to incidents of moral panic, particularly following reports of pedophilia associated with Satanic ritual abuse and day care sex abuse.[156] Instances of vigilantism have also been reported in response to public attention on convicted or suspected child sex offenders. In 2000, following a media campaign of "naming and shaming" suspected pedophiles in the UK, hundreds of residents took to the streets in protest against suspected pedophiles, eventually escalating to violent conduct requiring police intervention.[152] ## See also * Age disparity in sexual relationships * Child sexuality * Trafficking of children * Circles of Support and Accountability * Gerontophilia * List of paraphilias * Prevention Project Dunkelfeld ## References 1. ^ a b Gavin H (2013). Criminological and Forensic Psychology. SAGE Publications. p. 155. ISBN 978-1118510377. Retrieved July 7, 2018. 2. ^ a b c d Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, D.C.: American Psychological Association. p. vii. ISBN 978-1-4338-2926-0. 3. ^ Kail, RV; Cavanaugh JC (2010). Human Development: A Lifespan View (5th ed.). Cengage Learning. p. 296. ISBN 978-0495600374. 4. ^ a b c d e f g h Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. American Psychiatric Publishing. 2013. Retrieved July 25, 2013. 5. ^ a b c "The ICD-10 Classification of Mental and Behavioural Disorders Diagnostic criteria for research World" (PDF). World Health Organization/ICD-10. 1993. Section F65.4 "Paedophilia". Retrieved 2012-10-10. "B. A persistent or a predominant preference for sexual activity with a prepubescent child or children. C. The person is at least 16 years old and at least five years older than the child or children in B." 6. ^ a b c "ICD-11 for Mortality and Morbidity Statistics". World Health Organization/ICD-11. 2018. See section 6D32 Pedophilic disorder. Retrieved July 7, 2018. "Pedophilic disorder is characterized by a sustained, focused, and intense pattern of sexual arousal—as manifested by persistent sexual thoughts, fantasies, urges, or behaviours—involving pre-pubertal children. In addition, in order for Pedophilic Disorder to be diagnosed, the individual must have acted on these thoughts, fantasies or urges or be markedly distressed by them. This diagnosis does not apply to sexual behaviours among pre- or post-pubertal children with peers who are close in age." 7. ^ a b c d e f g h Fagan PJ, Wise TN, Schmidt CW, Berlin FS (November 2002). "Pedophilia". JAMA. 288 (19): 2458–65. doi:10.1001/jama.288.19.2458. PMID 12435259. 8. ^ a b c d e Ames, M. Ashley; Houston, David A. (August 1990). "Legal, social, and biological definitions of pedophilia". Archives of Sexual Behavior. 19 (4): 333–42. doi:10.1007/BF01541928. PMID 2205170. S2CID 16719658. 9. ^ a b c Lanning, Kenneth (2010). "Child Molesters: A Behavioral Analysis" (PDF). National Center for Missing & Exploited Children. Archived from the original (PDF) on 2010-12-24. 10. ^ a b c d e f Hall RC, Hall RC (2007). "A profile of pedophilia: definition, characteristics of offenders, recidivism, treatment outcomes, and forensic issues". Mayo Clin. Proc. 82 (4): 457–71. doi:10.4065/82.4.457. PMID 17418075. 11. ^ a b Blaney, Paul H.; Millon, Theodore (2009). Oxford Textbook of Psychopathology. Oxford Series in Clinical Psychology (2nd ed.). Cary, North Carolina: Oxford University Press, USA. p. 528. ISBN 978-0-19-537421-6. "Some cases of child molestation, especially those involving incest, are committed in the absence of any identifiable deviant erotic age preference." 12. ^ a b c Edwards, Michael. James, Marianne (ed.). "Treatment for Paedophiles; Treatment for Sex Offenders". Paedophile Policy and Prevention (12): 74–75. 13. ^ Cantor, James M.; McPhail, Ian V. (September 2016). "Non-offending Pedophiles". Current Sexual Health Reports. 8 (3): 121–128. doi:10.1007/s11930-016-0076-z. S2CID 148070920. 14. ^ a b Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, D.C.: American Psychological Association. pp. 72–74. ISBN 978-1-4338-2926-0. 15. ^ Goldman, Howard H. (2000). Review of General Psychiatry. New York: McGraw-Hill Professional Psychiatry. p. 374. ISBN 978-0-8385-8434-7. 16. ^ a b c d e Cohen, Lisa J.; Galynker, Igor (June 8, 2009). "Psychopathology and Personality Traits of Pedophiles". Psychiatric Times. 26 (6). Retrieved March 7, 2014. 17. ^ Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, D.C.: American Psychological Association. p. 101. ISBN 978-1-4338-2926-0. 18. ^ a b Seto, Michael (2008). "Pedophilia: Psychopathology and Theory". In Laws, D. Richard (ed.). Sexual Deviance: Theory, Assessment, and Treatment (2 ed.). New York City: The Guilford Press. p. 168. ISBN 9781593856052. 19. ^ a b c d Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, DC: American Psychological Association. p. xii, 186. ISBN 978-1-4338-2926-0. 20. ^ Liddell, H.G.; Scott, Robert (1959). Intermediate Greek-English Lexicon. Oxford, England: Oxford At The Clarendon Press. ISBN 978-0-19-910206-8. 21. ^ Greenberg, David M.; Bradford, John; Curry, Susan (1995). "Infantophilia—a new subcategory of pedophilia?: a preliminary study". The Bulletin of the American Academy of Psychiatry and the Law. 23 (1): 63–71. PMID 7599373. 22. ^ Goode, Sarah D. (2009). Understanding and Addressing Adult Sexual Attraction to Children: A Study of Paedophiles in Contemporary Society. London, England: Routledge. pp. 13–14. ISBN 978-1-135-25804-7. 23. ^ Laws, D. Richard; O'Donohue, William T. (2008). Sexual Deviance: Theory, Assessment, and Treatment. London, England: Guilford Press. p. 176. ISBN 978-1-59385-605-2. 24. ^ Blanchard R, Lykins AD, Wherrett D, Kuban ME, Cantor JM, Blak T, Dickey R, Klassen PE (June 2009). "Pedophilia, hebephilia, and the DSM-V". Arch Sex Behav. 38 (3): 335–50. doi:10.1007/s10508-008-9399-9. PMID 18686026. S2CID 14957904. 25. ^ a b c d e f g h i j k l m n Seto MC (2009). "Pedophilia". Annual Review of Clinical Psychology. 5: 391–407. doi:10.1146/annurev.clinpsy.032408.153618. PMID 19327034. 26. ^ a b c APA DSM-5 \| U 03 Pedophilic Disorder 27. ^ a b c S. Berlin, Frederick. "Interview with Frederick S. Berlin, M.D., Ph.D". Office of Media Relations. Archived from the original on June 23, 2011. Retrieved 2008-06-27. 28. ^ a b Cutler, Brian L., ed. (2008). "Pedophilia". Encyclopedia of Psychology and Law. 2. SAGE Publications, Inc. p. 549. ISBN 978-1-4129-5189-0. 29. ^ Berlin, Fred S. (2000). "Treatments to Change Sexual Orientation". Letter to the Editor. American Journal of Psychiatry. 157 (5): 838. doi:10.1176/appi.ajp.157.5.838. PMID 10784491. 30. ^ Wetzstein, Cheryl (October 31, 2013). "APA to correct manual: Pedophilia is not a 'sexual orientation'". The Washington Times. Washington DC: Washington Times LLC. Retrieved February 14, 2014. 31. ^ Marshall WL (1997). "The relationship between self-esteem and deviant sexual arousal in nonfamilial child molesters". Behavior Modification. 21 (1): 86–96. doi:10.1177/01454455970211005. PMID 8995044. S2CID 22205062. 32. ^ Okami, P. & Goldberg, A. (1992). "Personality Correlates of Pedophilia: Are They Reliable Indicators?", Journal of Sex Research, Vol. 29, No. 3, pp. 297–328. "For example, because an unknown percentage of true pedophiles may never act on their impulses or may never be arrested, forensic samples of sex offenders against minors clearly do not represent the population of "pedophiles", and many such persons apparently do not even belong to the population of "pedophiles"." 33. ^ a b Seto MC (2004). "Pedophilia and sexual offenses against children". Annu Rev Sex Res. 15: 321–61. PMID 16913283. 34. ^ Cohen LJ, McGeoch PG, Watras-Gans S, Acker S, Poznansky O, Cullen K, Itskovich Y, Galynker I (October 2002). "Personality impairment in male pedophiles". Journal of Clinical Psychiatry. 63 (10): 912–9. doi:10.4088/JCP.v63n1009. PMID 12416601. 35. ^ Strassberg, Donald S., Eastvold, Angela, Kenney, J. Wilson, Suchy, Yana (2012). "Psychopathy among pedophilic and nonpedophilic child molesters". Child Abuse & Neglect. 36 (4): 379–382. doi:10.1016/j.chiabu.2011.09.018. PMID 22571910.CS1 maint: multiple names: authors list (link) 36. ^ Suchy, Yana; Whittaker, Wilson J.; Strassberg, Donald S.; Eastvold, Angela (2009). "Facial and prosodic affect recognition among pedophilic and nonpedophilic criminal child molesters". Sexual Abuse: A Journal of Research and Treatment. 21 (1): 93–110. doi:10.1177/1079063208326930. PMID 19218480. S2CID 25360637. 37. ^ Wilson G. D.; Cox D. N. (1983). "Personality of paedophile club members". Personality and Individual Differences. 4 (3): 323–329. doi:10.1016/0191-8869(83)90154-X. 38. ^ a b c Jahnke, S., Hoyer, J. (2013). "Stigma against people with pedophilia: A blind spot in stigma research?". International Journal of Sexual Health. 25 (3): 169–184. doi:10.1080/19317611.2013.795921. S2CID 145656359.CS1 maint: multiple names: authors list (link) 39. ^ Lawson L (2003). "Isolation, gratification, justification: offenders' explanations of child molesting". Issues in Mental Health Nursing. 24 (6–7): 695–705. doi:10.1080/01612840305328. PMID 12907384. S2CID 13188168. 40. ^ Mihailides S, Devilly GJ, Ward T (2004). "Implicit cognitive distortions and sexual offending". Sexual Abuse: A Journal of Research and Treatment. 16 (4): 333–350. doi:10.1177/107906320401600406. PMID 15560415. S2CID 220359426. 41. ^ a b Seto MC, Cantor JM, Blanchard R (August 2006). "Child pornography offenses are a valid diagnostic indicator of pedophilia". J Abnorm Psychol. 115 (3): 610–5. CiteSeerX 10.1.1.606.7677. doi:10.1037/0021-843X.115.3.610. PMID 16866601. "The results suggest child pornography offending is a stronger diagnostic indicator of pedophilia than is sexually offending against child victims" 42. ^ a b Lanning, Kenneth V. (2010). "Child Molesters: A Behavioral Analysis, Fifth Edition" (PDF). National Center for Missing and Exploited Children: 79. Archived from the original (PDF) on 2010-12-24. Cite journal requires `\|journal=` (help) 43. ^ Crosson-Tower, Cynthia (2005). Understanding child abuse and neglect. Allyn & Bacon. p. 208. ISBN 978-0-205-40183-3. 44. ^ Richard Wortley; Stephen Smallbone. "Child Pornography on the Internet" (PDF). Problem-Oriented Guides for Police. No. 41: 14–16. Archived from the original (PDF) on 2015-01-07. 45. ^ Levesque, Roger J. R. (1999). Sexual Abuse of Children: A Human Rights Perspective. Indiana University. p. 64. ISBN 978-0-253-33471-8. 46. ^ Crosson-Tower, Cynthia (2005). Understanding child abuse and neglect. Allyn & Bacon. pp. 198–200. ISBN 978-0-205-40183-3. 47. ^ Lanning, Kenneth V. (2010). "Child Molesters: A Behavioral Analysis, Fifth Edition" (PDF). National Center for Missing and Exploited Children: 107. Archived from the original (PDF) on 2010-12-24. Cite journal requires `\|journal=` (help) 48. ^ Quayle, E.; Taylor, M. (2002). "Child pornography and the internet: Assessment Issues". British Journal of Social Work. 32 (7): 867. doi:10.1093/bjsw/32.7.863. 49. ^ a b Blanchard R.; Kolla N. J.; Cantor J. M.; Klassen P. E.; Dickey R.; Kuban M. E.; Blak T. (2007). "IQ, handedness, and pedophilia in adult male patients stratified by referral source". Sexual Abuse: A Journal of Research and Treatment. 19 (3): 285–309. doi:10.1177/107906320701900307. PMID 17634757. S2CID 220359453. 50. ^ a b c Cantor JM, Blanchard R, Christensen BK, Dickey R, Klassen PE, Beckstead AL, Blak T, Kuban ME (2004). "Intelligence, memory, and handedness in pedophilia". Neuropsychology. 18 (1): 3–14. doi:10.1037/0894-4105.18.1.3. PMID 14744183. 51. ^ Cantor JM, Blanchard R, Robichaud LK, Christensen BK (2005). "Quantitative reanalysis of aggregate data on IQ in sexual offenders". Psychological Bulletin. 131 (4): 555–568. CiteSeerX 10.1.1.557.6376. doi:10.1037/0033-2909.131.4.555. PMID 16060802. 52. ^ Cantor JM, Klassen PE, Dickey R, Christensen BK, Kuban ME, Blak T, Williams NS, Blanchard R (2005). "Handedness in pedophilia and hebephilia". Archives of Sexual Behavior. 34 (4): 447–459. doi:10.1007/s10508-005-4344-7. PMID 16010467. S2CID 6427342. 53. ^ Bogaert AF (2001). "Handedness, criminality, and sexual offending". Neuropsychologia. 39 (5): 465–469. doi:10.1016/S0028-3932(00)00134-2. PMID 11254928. S2CID 28513717. 54. ^ Cantor JM, Kuban ME, Blak T, Klassen PE, Dickey R, Blanchard R (2006). "Grade failure and special education placement in sexual offenders' educational histories". Archives of Sexual Behavior. 35 (6): 743–751. doi:10.1007/s10508-006-9018-6. PMID 16708284. S2CID 24164499. 55. ^ Cantor JM, Kuban ME, Blak T, Klassen PE, Dickey R, Blanchard R (2007). "Physical height in pedophilic and hebephilic sexual offenders". Sex Abuse. 19 (4): 395–407. doi:10.1007/s11194-007-9060-5. PMID 17952597. S2CID 322977. 56. ^ McPhail, Ian V.; Cantor, James M. (2015-04-03). "Pedophilia, Height, and the Magnitude of the Association: A Research Note". Deviant Behavior. 36 (4): 288–292. doi:10.1080/01639625.2014.935644. ISSN 0163-9625. S2CID 144724465. 57. ^ a b Blanchard R, Christensen BK, Strong SM, Cantor JM, Kuban ME, Klassen P, Dickey R, Blak T (2002). "Retrospective self-reports of childhood accidents causing unconsciousness in phallometrically diagnosed pedophiles". Archives of Sexual Behavior. 31 (6): 511–526. doi:10.1023/A:1020659331965. PMID 12462478. S2CID 11268132. 58. ^ Blanchard R, Kuban ME, Klassen P, Dickey R, Christensen BK, Cantor JM, Blak T (2003). "Self-reported injuries before and after age 13 in pedophilic and non-pedophilic men referred for clinical assessment". Archives of Sexual Behavior. 32 (6): 573–581. doi:10.1023/A:1026093612434. PMID 14574100. S2CID 37671245. 59. ^ a b Cantor JM, Kabani N, Christensen BK, Zipursky RB, Barbaree HE, Dickey R, Klassen PE, Mikulis DJ, Kuban ME, Blak T, Richards BA, Hanratty MK, Blanchard R (2008). "Cerebral white matter deficiencies in pedophilic men". Journal of Psychiatric Research. 42 (3): 167–183. doi:10.1016/j.jpsychires.2007.10.013. PMID 18039544. 60. ^ Schiffer B, Peschel T, Paul T, Gizewski E, Forsting M, Leygraf N, Schedlowski M, Krueger TH (2007). "Structural brain abnormalities in the frontostriatal system and cerebellum in pedophilia". J Psychiatr Res. 41 (9): 753–62. doi:10.1016/j.jpsychires.2006.06.003. PMID 16876824. 61. ^ Schiltz K, Witzel J, Northoff G, Zierhut K, Gubka U, Fellmann H, Kaufmann J, Tempelmann C, Wiebking C, Bogerts B (2007). "Brain pathology in pedophilic offenders: Evidence of volume reduction in the right amygdala and related diencephalic structures". Archives of General Psychiatry. 64 (6): 737–746. doi:10.1001/archpsyc.64.6.737. PMID 17548755. 62. ^ Joyal, CC, Plante-Beaulieu, J. & De Chanterac, A. (2014). "The neuropsychology of sexual offenders: A meta-analysis". Journal of Sexual Abuse. 26 (2): 149–177. doi:10.1177/1079063213482842. PMID 23567470. S2CID 14787096. "The distinction between nonpedophilic child molesters and exclusive pedophile child molesters, for instance, could be crucial in neuropsychology because the latter seem to be less cognitively impaired (Eastvold et al., 2011; Schiffer & Vonlaufen, 2011; Suchy et al., 2009). Pedophilic child molesters might perform as well as controls (and better than nonpedophilic child molesters) on a wide variety of neuropsychological measures when mean IQ and other socioeconomic factors are similar (Schiffer & Vonlaufen, 2011). In fact, some pedophiles have higher IQ levels and more years of education compared with the general population (Langevin et al., 2000; Lothstein, 1999; Plante & Aldridge, 2005)."CS1 maint: multiple names: authors list (link) 63. ^ Schiffer, B., & Vonlaufen, C. (2011). "Executive dysfunctions in pedophilic and nonpedophilic child molesters". Journal of Sexual Medicine. 8 (7): 1975–1984. doi:10.1111/j.1743-6109.2010.02140.x. PMID 21210954.CS1 maint: multiple names: authors list (link) 64. ^ Gaffney GR, Lurie SF, Berlin FS (September 1984). "Is there familial transmission of pedophilia?". J. Nerv. Ment. Dis. 172 (9): 546–8. doi:10.1097/00005053-198409000-00006. PMID 6470698. S2CID 40552527. 65. ^ Azizian, Allen (2015). "Cognitional Impairment: Is There a Role for Cognitive Assessment in the Treatment of Individuals Civilly Committed Pursuant to the Sexually Violent Predator Act?" (PDF). Sexual Abuse: A Journal of Research and Treatment. 28 (1–15): 755–769. doi:10.1177/1079063215570757. PMID 25698358. S2CID 6007407. Archived from the original on June 11, 2015. Retrieved 27 April 2016.CS1 maint: unfit URL (link) 66. ^ Walter; et al. (2007). "Pedophilia Is Linked to Reduced Activation in Hypothalamus and Lateral Prefrontal Cortex During Visual Erotic Stimulation". Biological Psychiatry. 62 (6): 698–701. doi:10.1016/j.biopsych.2006.10.018. PMID 17400196. S2CID 6971495. 67. ^ Schiffer B, Paul T, Gizewski E, Forsting M, Leygraf N, Schedlowski M, Kruger TH (May 2008). "Functional brain correlates of heterosexual paedophilia". NeuroImage. 41 (1): 80–91. doi:10.1016/j.neuroimage.2008.02.008. PMID 18358744. S2CID 3350912. 68. ^ a b Blanchard, R., Cantor, J. M., & Robichaud, L. K. (2006). Biological factors in the development of sexual deviance and aggression in males. In Howard E. Barbaree; William L. Marshall (19 June 2008). The Juvenile Sex Offender. Guilford Press. p. 77. ISBN 978-1-59385-978-7. 69. ^ Rahman Q, Symeonides DJ (February 2007). "Neurodevelopmental Correlates of Paraphilic Sexual Interests in Men". Archives of Sexual Behavior. 37 (1): 166–172. doi:10.1007/s10508-007-9255-3. PMID 18074220. S2CID 22274418. 70. ^ a b See section F65.4 Paedophilia. "International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) Version for 2010". ICD-10. Retrieved November 17, 2012. 71. ^ Pedophilia Archived 2006-05-08 at the Wayback Machine DSM at the Medem Online Medical Library 72. ^ O'Donohue W, Regev LG, Hagstrom A (2000). "Problems with the DSM-IV diagnosis of pedophilia". Sex Abuse. 12 (2): 95–105. doi:10.1023/A:1009586023326. PMID 10872239. S2CID 195287902. 73. ^ Green R (2002). "Is pedophilia a mental disorder?". Archives of Sexual Behavior. 31 (6): 467–471. doi:10.1023/a:1020699013309. PMID 12462476. S2CID 7774415. Archived from the original on 2010-10-12. 74. ^ Moulden HM, Firestone P, Kingston D, Bradford J (2009). "Recidivism in pedophiles: an investigation using different diagnostic methods". Journal of Forensic Psychiatry & Psychology. 20 (5): 680–701. doi:10.1080/14789940903174055. S2CID 144622835. 75. ^ Feelgood S, Hoyer J (2008). "Child molester or paedophile? Sociolegal versus psychopathological classification of sexual offenders against children". Journal of Sexual Aggression. 14 (1): 33–43. doi:10.1080/13552600802133860. S2CID 145471750. 76. ^ Blanchard R (April 2010). "The DSM diagnostic criteria for pedophilia". Arch Sex Behav. 39 (2): 304–16. doi:10.1007/s10508-009-9536-0. PMID 19757012. S2CID 20213586. 77. ^ Blanchard R, Lykins AD, Wherrett D, Kuban ME, Cantor JM, Blak T, Dickey R, Klassen PE (2009). "Pedophilia, Hebephilia, and the DSM-V". Archives of Sexual Behavior. 38 (3): 335–350. doi:10.1007/s10508-008-9399-9. PMID 18686026. S2CID 14957904. 78. ^ Karen Franklin (2 December 2012). "Psychiatry Rejects Novel Sexual Disorder "Hebephilia"". Psychology Today. USA. 79. ^ a b "Paraphilic Disorders" (PDF). American Psychiatric Publishing. 2013. Archived from the original (PDF) on July 24, 2016. Retrieved July 8, 2013. 80. ^ O'Donohue W (Jun 2010). "A critique of the proposed DSM-V diagnosis of pedophilia". Arch Sex Behav. 39 (3): 587–90. doi:10.1007/s10508-010-9604-5. PMID 20204487. S2CID 30900698. 81. ^ a b Barbaree, H. E., and Seto, M. C. (1997). Pedophilia: Assessment and Treatment. Sexual Deviance: Theory, Assessment, and Treatment. 175–193. 82. ^ Seto MC, Ahmed AG (2014). "Treatment and management of child pornography use". Psychiatric Clinics of North America. 37 (2): 207–214. doi:10.1016/j.psc.2014.03.004. PMID 24877707. 83. ^ Camilleri, Joseph A.; Quinsey, Vernon L. (2008). "Pedophilia: Assessment and Treatment". In Laws, D. Richard (ed.). Sexual Deviance: Theory, Assessment, and Treatment. The Guilford Press. p. 193. 84. ^ Berlin, Fred S. (December 2002). "Peer Commentaries on Green (2002) and Schmidt (2002) – Pedophilia: When Is a Difference a Disorder?" (PDF). Archives of Sexual Behavior. 31 (6): 479–480. doi:10.1023/A:1020603214218. S2CID 102340546. Archived from the original (PDF) on 2008-10-29. Retrieved 2009-12-17. 85. ^ Rice ME, Harris GT (2003). "The size and signs of treatment effects in sex offender therapy". Annals of the New York Academy of Sciences. 989 (1): 428–40. Bibcode:2003NYASA.989..428R. doi:10.1111/j.1749-6632.2003.tb07323.x. PMID 12839916. 86. ^ a b Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, DC: American Psychological Association. p. 171. 87. ^ a b Dennis JA, Khan O, Ferriter M, Huband N, Powney MJ, Duggan C (2012). "Psychological interventions for adults who have sexually offended or are at risk of offending". Cochrane Database of Systematic Reviews. 12 (12): CD007507. doi:10.1002/14651858.CD007507.pub2. PMID 23235646. 88. ^ Lösel F, Schmucker M (2005). "The effectiveness of treatment for sexual offenders: a comprehensive meta-analysis". Journal of Experimental Criminology. 1 (1): 117–46. doi:10.1007/s11292-004-6466-7. S2CID 145253074. 89. ^ Hanson RK, Gordon A, Harris AJ, Marques JK, Murphy W, et al. (2002). "First report of the collaborative outcome data project on the effectiveness of treatment for sex offenders". Sexual Abuse. 14 (2): 169–94. doi:10.1177/107906320201400207. PMID 11961890. S2CID 34192852. 90. ^ Rice ME, Harris GT (2012). "Treatment for adult sex offenders: may we reject the null hypothesis?". In Harrison K, Rainey B (eds.). Handbook of Legal & Ethical Aspects of Sex Offender Treatment & Management. London, England: Wiley-Blackwell. 91. ^ Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, DC: American Psychological Association. p. 175. ISBN 978-1-4338-2926-0. 92. ^ Barbaree, H. E., Bogaert, A. F., & Seto, M. C. (1995). Sexual reorientation therapy for pedophiles: Practices and controversies. In L. Diamant & R. D. McAnulty (Eds.), The psychology of sexual orientation, behavior, and identity: A handbook (pp. 357–383). Westport, CT: Greenwood Press. 93. ^ Barbaree, H. C., & Seto, M. C. (1997). Pedophilia: Assessment and treatment. In D. R. Laws & W. T. O'Donohue (eds.), Sexual deviance: Theory, assessment and treatment (pp. 175–193). New York: Guildford Press. 94. ^ Maguth Nezu C.; Fiore A. A.; Nezu A. M (2006). Problem Solving Treatment for Intellectually Disabled Sex Offenders. International Journal of Behavioral Consultation and Therapy. 2. pp. 266–275. doi:10.1002/9780470713488.ch6. ISBN 9780470713488. 95. ^ a b Camilleri, Joseph A., and Quinsey, Vernon L. (2008). "Pedophilia: Assessment and Treatment". In Laws, D. Richard (ed.). Sexual Deviance: Theory, Assessment, and Treatment, 2nd edition. The Guilford Press. pp. 199–200.CS1 maint: multiple names: authors list (link) 96. ^ a b Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, DC: American Psychological Association. pp. 177–181. 97. ^ Cohen LJ, Galynker II (2002). "Clinical features of pedophilia and implications for treatment". Journal of Psychiatric Practice. 8 (5): 276–89. doi:10.1097/00131746-200209000-00004. PMID 15985890. S2CID 22782583. 98. ^ Guay, DR (2009). "Drug treatment of paraphilic and nonparaphilic sexual disorders". Clinical Therapeutics. 31 (1): 1–31. doi:10.1016/j.clinthera.2009.01.009. PMID 19243704. 99. ^ a b "Anti-androgen therapy and surgical castration". Association for the Treatment of Sexual Abusers. 1997. Archived from the original on August 29, 2011. 100. ^ Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, DC: American Psychological Association. pp. 181–182, 192. 101. ^ "Prague Urged to End Castration of Sex Offenders". DW.DE. 2009-02-05. Retrieved 2015-01-19. 102. ^ Howells, K. (1981). "Adult sexual interest in children: Considerations relevant to theories of aetiology", Adult sexual interest in children. 55–94. 103. ^ Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, DC: American Psychological Association. p. 4. 104. ^ Suchy, Y., Whittaker, W.J., Strassberg, D., & Eastvold, A. (2009). "Facial and Prosodic Affect Recognition Among Pedophilic and Nonpedophilic Criminal Child Molesters". Sexual Abuse: A Journal of Research and Treatment. 21 (1): 93–110. doi:10.1177/1079063208326930. PMID 19218480. S2CID 25360637.CS1 maint: multiple names: authors list (link) 105. ^ a b Schaefer, G. A., Mundt, I. A., Feelgood, S., Hupp, E., Neutze, J., Ahlers, Ch. J., Goecker, D., Beier, K. M. (2010). "Potential and Dunkelfeld offenders: Two neglected target groups for prevention of child sexual abuse". International Journal of Law & Psychiatry. 33 (3): 154–163. doi:10.1016/j.ijlp.2010.03.005. PMID 20466423.CS1 maint: multiple names: authors list (link) 106. ^ Seto, M. C., Cantor, J. M., & Blanchard, R. (2006). "Child pornography offenses are a valid diagnostic indicator of pedophilia". Journal of Abnormal Psychology. 115 (3): 612. CiteSeerX 10.1.1.606.7677. doi:10.1037/0021-843x.115.3.610. PMID 16866601.CS1 maint: multiple names: authors list (link) 107. ^ Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, DC: American Psychological Association. p. 123. 108. ^ Blanchard, R., Kuban, M. E., Blak, T., Cantor, J. M., Klassen, P., & Dickey, R. (2006). "Phallometric comparison of pedophilic interest in nonadmitting sexual offenders against stepdaughters, biological daughters, other biologically related girls, and unrelated girls". Sexual Abuse: A Journal of Research and Treatment. 18 (1): 1–14. CiteSeerX 10.1.1.1016.1030. doi:10.1177/107906320601800101. PMID 16598663. S2CID 220355661.CS1 maint: multiple names: authors list (link) 109. ^ Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, DC: American Psychological Association. pp. 47–48, 66. 110. ^ Kärgel, C., Massau, C., Weiß, S., Walter, M., Kruger, T. H., & Schiffer, B. (2015). "Diminished Functional Connectivity on the Road to Child Sexual Abuse in Pedophilia". The Journal of Sexual Medicine. 12 (3): 783–795. doi:10.1111/jsm.12819. PMID 25615561.CS1 maint: multiple names: authors list (link) 111. ^ Abel, G. G., Mittleman, M. S., & Becker, J. V. (1985). "Sex offenders: Results of assessment and recommendations for treatment". In M. H. Ben-Aron, S. J. Hucker, & C. D. Webster (Eds.), Clinical criminology: The assessment and treatment of criminal behavior (pp. 207–220). Toronto, Canada: M & M Graphics. 112. ^ Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, DC: American Psychological Association. pp. 64, 189. 113. ^ Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, DC: American Psychological Association. p. 13. 114. ^ a b c d Von Krafft-Ebing, Richard (1922). Psychopathia Sexualis. Translated to English by Francis Joseph Rebman. Medical Art Agency. pp. 552–560. ISBN 978-1-871592-55-9. 115. ^ a b Janssen, D.F. (2015). ""Chronophilia": Entries of Erotic Age Preference into Descriptive Psychopathology". Medical History. 59 (4): 575–598. doi:10.1017/mdh.2015.47. ISSN 0025-7273. PMC 4595948. PMID 26352305. 116. ^ Roudinesco, Élisabeth (2009). Our dark side: a history of perversion, p. 144. Polity, ISBN 978-0-7456-4593-3 117. ^ Freud, Sigmund Three Contributions to the Theory of Sex Mobi Classics pages 18–20 118. ^ Forel, Auguste (1908). The Sexual Question: A scientific, psychological, hygienic and sociological study for the cultured classes. Translated to English by C.F. Marshall, MD. Rebman. pp. 254–255. 119. ^ American Psychiatric Association Committee on Nomenclature and Statistics (1952). Diagnostic and statistical manual of mental disorders (1st ed.). Washington, D.C: The Association. p. 39. 120. ^ American Psychiatric Association: Committee on Nomenclature and Statistics (1980). Diagnostic and statistical manual of mental disorders (3rd ed.). Washington, D.C: American Psychiatric Association. p. 271. 121. ^ Diagnostic and statistical manual of mental disorders: DSM-III-R. Washington, DC: American Psychiatric Association. 1987. ISBN 978-0-89042-018-8. 122. ^ "Child abuse investigation impact" (PDF). Metropolitan Police Service (met.police.uk). Archived from the original (PDF) on April 19, 2014. Retrieved April 18, 2014. 123. ^ Holmes, Ronald M. (2008-12-01). Profiling Violent Crimes: An Investigative Tool. Sage Publications. ISBN 978-1-4129-5998-8. 124. ^ Lanning, Kenneth V. (2010). "Child Molesters: A Behavioral Analysis, Fifth Edition" (PDF). National Center for Missing and Exploited Children: 16–17, 19–20. Archived from the original (PDF) on 2010-12-24. Cite journal requires `\|journal=` (help) 125. ^ Morris, Grant H. (2002). "Commentary: Punishing the Unpunishable—The Abuse of Psychiatry to Confine Those We Love to Hate" (PDF). Journal of the American Academy of Psychiatry and the Law. 30 (4): 556–562. PMID 12539913. 126. ^ a b Holland, Jesse J. (May 17, 2010). "Court: Sexually dangerous can be kept in prison". Associated Press. Archived from the original on May 20, 2010. Retrieved May 16, 2010. 127. ^ "Psychological Evaluation for the Courts, Second Edition – A Handbook for Mental Health Professionals and Lawyers – 9.04 Special Sentencing Provisions (b) Sexual Offender Statutes". Guilford.com. Archived from the original on 2006-12-11. Retrieved 2007-10-19. 128. ^ Cripe, Clair A; Pearlman, Michael G (2005). Legal aspects of corrections management. ISBN 978-0-7637-2545-7. 129. ^ Ramsland, Katherine M; McGrain, Patrick Norman (2010). Inside the minds of sexual predators. ISBN 978-0-313-37960-4. 130. ^ Liptak, Adam (2010-05-17). "Extended Civil Commitment of Sex Offenders Is Upheld". The New York Times. 131. ^ Barker, Emily (2009). "The Adam Walsh Act: Un-Civil Commitment". Hastings Constitutional Law Quarterly. 37 (1): 145. SSRN 1496934. 132. ^ First, Michael B., Halon, Robert L. (2008). "Use of DSM Paraphilia Diagnoses in Sexually Violent Predator Commitment Cases" (PDF). Journal of the American Academy of Psychiatry and the Law. 36 (4): 443–54. PMID 19092060.CS1 maint: multiple names: authors list (link) 133. ^ Jahnke, S., Imhoff, R., Hoyer, J. (2015). "Stigmatization of People with Pedophilia: Two Comparative Surveys". Archives of Sexual Behavior. 44 (1): 21–34. doi:10.1007/s10508-014-0312-4. PMID 24948422. S2CID 36369240.CS1 maint: multiple names: authors list (link) 134. ^ Neuillya, M.; Zgobab, K. (2006). "Assessing the Possibility of a Pedophilia Panic and Contagion Effect Between France and the United States". Victims & Offenders. 1 (3): 225–254. doi:10.1080/15564880600626122. S2CID 144284647. 135. ^ Seto, Michael (2008). Pedophilia and Sexual Offending Against Children. Washington, DC: American Psychological Association. p. viii. 136. ^ McCartan, K. (2004). "'Here There Be Monsters': the public's perception of paedophiles with particular reference to Belfast and Leicester". Medicine, Science and the Law. 44 (4): 327–42. doi:10.1258/rsmmsl.44.4.327. PMID 15573972. S2CID 21085787. 137. ^ "Pedophilia". Encyclopædia Britannica. Retrieved July 19, 2015. 138. ^ Guzzardi, Will (2010-01-06). "Andy Martin, GOP Senate Candidate, Calls Opponent Mark Kirk A "De Facto Pedophile"". Huffington Post. Retrieved 15 January 2010. 139. ^ a b Jenkins, Philip (2006). Decade of Nightmares: The End of the Sixties and the Making of Eighties America. Oxford University Press. p. 120. ISBN 978-0-19-517866-1. 140. ^ Spiegel, Josef (2003). Sexual Abuse of Males: The Sam Model of Theory and Practice. Routledge. pp. 5, p9. ISBN 978-1-56032-403-4. 141. ^ a b c d Eichewald, Kurt (August 21, 2006). "From Their Own Online World, Pedophiles Extend Their Reach". New York Times. 142. ^ Frits Bernard. "The Dutch Paedophile Emancipation Movement". Paidika: The Journal of Paedophilia. 1 (2, (Autumn 1987), p. 35–45). Archived from the original on January 2, 2016. "Heterosexuality, homosexuality, bisexuality and paedophilia should be considered equally valuable forms of human behavior." 143. ^ Jenkins, Philip (1992). Intimate Enemies: Moral Panics in Contemporary Great Britain. Aldine Transaction. p. 75. ISBN 978-0-202-30436-6. "In the 1970s, the pedophile movement was one of several fringe groups whose cause was to some extent espoused in the name of gay liberation." 144. ^ Stanton, Domna C. (1992). Discourses of Sexuality: From Aristotle to AIDS. University of Michigan Press. p. 405. ISBN 978-0-472-06513-4. 145. ^ a b Hagan, Domna C.; Marvin B. Sussman (1988). Deviance and the family. Haworth Press. p. 131. ISBN 978-0-86656-726-8. 146. ^ Benoit Denizet-Lewis (2001). "Boy Crazy", Boston Magazine. 147. ^ Trembaly, Pierre (2002). "Social interactions among paedophiles" Archived 2009-11-22 at the Wayback Machine 148. ^ "Virtuous Pedophiles – Welcome". virped.org. Retrieved September 12, 2015. 149. ^ Clark-Flory, Tracy (June 20, 2012). "Meet pedophiles who mean well". Salon. Retrieved September 12, 2015. 150. ^ "Virtuous Pedophiles". 151. ^ "Global Crime Report – INVESTIGATION – Child porn and the cybercrime treaty part 2 – BBC World Service". bbc.co.uk. 152. ^ a b Families flee paedophile protests August 9, 2000. Retrieved January 24, 2008. 153. ^ Dutch paedophiles set up political party, May 30, 2006. Retrieved January 2008. 154. ^ "The Perverted Justice Foundation Incorporated – A note from our foundation to you". Perverted-Justice. Retrieved March 16, 2012. 155. ^ Salkin, Allen; Happy Blitt (2006-12-13). "Web Site Hunts Pedophiles and TV Goes Along". The New York Times. New York, New York. Retrieved March 16, 2012. "'Every waking minute he's on that computer,' said his mother, Mary Erck-Heard, 46, who raised her son after they fled his father, whom she described as alcoholic. Mr. Von Erck legally changed his name from Phillip John Eide, taking his maternal grandfather's family name, Erck, and adding the Von." 156. ^ Jewkes, Yvonne (2004). Media and crime. Thousand Oaks, California: Sage Publications. pp. 76–77. ISBN 978-0-7619-4765-3. ## Further reading * Gladwell, Malcolm. "In Plain View." ("Jerry Sandusky and the Mind of a Pedophile") The New Yorker. September 24, 2012. * Philby, Charlotte. "Female sexual abuse: The untold story of society's last taboo." The Independent. Saturday August 8, 2009. * Bleyer, Jennifer. "How Can We Stop Pedophiles? Stop treating them like monsters." Slate. Monday September 24, 2012. * Fong, Diana. Editor: Nancy Isenson. "'If I'm attracted to children, I must be a monster'." Die Welt. May 29, 2013. ## External links Look up pedophilia in Wiktionary, the free dictionary. Wikimedia Commons has media related to Pedophilia. Wikiquote has quotations related to: Pedophilia * Understanding MRI research on pedophilia * Pedophilia: Myths, Realities and Treatments ( Page will play audio when loaded) * Indictment from Operation Delego (PDF) (Archive) * Virtuous Pedophiles, online support for non-offending pedophiles working to remain offence-free. * HelpWantedPrevention.org, an online self-help course from Johns Hopkins University for managing attraction to children Classification D * ICD-10: F65.4 * ICD-9-CM: 302.2 * MeSH: D010378 * v * t * e Pedophilia and child sexual abuse Associated chronophilias * Hebephilia * Ephebophilia Behavior and legal aspects * Age of consent reform * Child pornography * Hurtcore * Child erotica * Simulated * Legality * Legal status of drawn pornography depicting minors * Child grooming * Causes of clerical child abuse * Commercial sexual exploitation of children * Child prostitution * Child sex tourism * Child trafficking * Cybersex trafficking * Child marriage * Marriageable age * Pederasty By country * Afghanistan * Australia * Egypt * Nigeria * United Kingdom Treatment methods * Chemical castration * Castration * Cognitive behavioral therapy Research and support groups * Association for the Treatment of Sexual Abusers * Circles of Support and Accountability * Silentlambs * Survivors Network of those Abused by Priests * Virtuous Pedophiles Prevention organizations * Association for the Treatment of Sexual Abusers * Child Exploitation and Online Protection Command * Jewish Community Watch * Prevention Project Dunkelfeld * Special Rapporteur on the sale of children, child prostitution and child pornography * The Awareness Center * Tzedek Social views * Anti-pedophile activism * Creep Catchers * Dark Justice * Perverted-Justice * Sweetie (internet avatar) * Pedophile advocacy groups Related * Anglican Communion sexual abuse cases * Catholic Church sexual abuse cases * by country * debate * media coverage * Society of Jesus * Child sexual abuse in New York City 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[ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Pedophilia	c0030764	3,998	wikipedia	https://en.wikipedia.org/wiki/Pedophilia	2021-01-18T19:03:56	{"mesh": ["D010378"], "umls": ["C0030764"], "wikidata": ["Q8388"]}
Disorder where there is enlargement of both legs due to deposits of fat under the skin Lipedema Other namesLipoedema, lipödem, lipalgia, adiposalgia, adipoalgesia, adiposis dolorosa, lipomatosis dolorosa of the legs, lipohypertrophy dolorosa, painful column leg, painful lipedema syndrome A very advanced case of lipedema of the right leg (the knee is pointing to the right and is concealed by the overhanging lipedema). SpecialtyVascular medicine SymptomsIncreased fat deposits under the skin in the legs, easy bruising, pain[1] CausesUnknown[1] Risk factorsOverweight[1] Differential diagnosislipohypertrophy, chronic venous insufficiency, lymphedema[1] TreatmentPhysiotherapy, exercise[1] FrequencyUp to 11% of women[1] Lipedema is a disorder where there is enlargement of both legs due to deposits of fat under the skin.[1] Typically it gets worse over time, pain may be present, and sufferers bruise easily.[1] In severe cases the trunk and upper body may be involved.[1] Lipedema is commonly misdiagnosed.[2] The cause is unknown but is believed to involve genetics and hormonal factors.[1] It often runs in families,[1] and is hormone related. Other conditions that may present similarly include lipohypertrophy, chronic venous insufficiency, and lymphedema.[1] A number of treatments may be useful including physiotherapy and exercise. Physiotherapy may help to preserve mobility for a little longer than would otherwise be the case. Exercise, only as much as the patient is able to do without causing damage to the joints, may help with overall fitness but will not prevent progression of the disease.[1] While surgery can remove fat tissue it can also damage lymphatic vessels.[1] Treatment does not typically result in complete resolution.[3] It is estimated to affect up to 11% of women.[1] Onset is typically during puberty, pregnancy, or menopause.[1] Many clinicians either are unaware of the disease or have a hard time differentiating it from obesity or other types of edema.[4] ## Contents * 1 Diagnosis * 1.1 Differential diagnosis * 1.2 Lipedema stages * 1.3 Similar conditions * 1.3.1 Lipo-lymphedema * 1.3.2 Dercum's disease * 2 Treatment * 3 Prognosis * 4 Epidemiology * 5 History * 6 See also * 7 References * 8 External links ## Diagnosis[edit] ### Differential diagnosis[edit] [5][6][7][8][9][2] Lipedema Lipo-lymphedema Lymphedema Obesity Venous insufficiency/venous stasis Symptoms: Fat deposits / swelling in legs and arms not in hands or feet; hands and feet may be affected as the disease progresses. Fat deposits / swelling widespread in legs/arms/torso Fat deposits / swelling in one limb including hands and feet Fat deposits widespread Swelling near ankles; brownish discoloration of lower legs (hemosiderin deposits). Minimal swelling possible. Male/female: F F F/M F/M F/M Onset: Around hormonal shifts (puberty, pregnancy, menopause) Around hormonal shifts After surgery that affects lymphatic system, or at birth Any age Around onset of obesity, diabetes, pregnancy, hypertension Effects of diet: Restricting calories ineffective Restricting calories ineffective Restricting calories ineffective Diets and weight loss strategies often effective No relation to caloric intake Presence of edema: Non-pitting edema Much edema; some pitting; some fibrosis Pitting edema No edema Often edema, but can also occur without edema in earlier stages Presence of Stemmer Sign: Stemmer's Sign negative Stemmer's Sign positive Stemmer's Sign positive Stemmer's Sign negative Stemmer's sign may or may not be present in lymphedema/lipolymphedema Presence of pain: Pain in affected areas likely Pain in affected areas No pain initially No pain Pain is likely Affected population: Best estimate is 11% adult women (study done in Germany) Unknown; best estimate is a few percent of adult women Low ≥30% of US adults >30% of US adults Presence of cellulitis: No history of cellulitis Likely history of cellulitis Possible history of cellulitis Often itching +/- discoloration mistaken for cellulitis Family history: Family history likely Family history of lipedema likely Family history not likely unless primary lymphedema Family history likely Very likely family history ### Lipedema stages[edit] Lipedema is classified by stage: Stage 1: Normal skin surface with enlarged hypodermis (lipedema fat). Stage 2: Uneven skin with indentations in fat and larger hypodermal masses (lipomas). Stage 3: Bulky extrusions of skin and fat cause large deformations especially on the thighs and around the knees. These large extrusions of tissue drastically inhibit mobility.[10][11] ### Similar conditions[edit] Lipedema is often underdiagnosed due to the difficulty in differentiating it from lymphedema, obesity, or other edemas. Many clinicians are unaware of the disease.[4] Trayes 2013 published some tools including tables and a flow chart that can be used to diagnose lipedema and other edemas.[9] #### Lipo-lymphedema[edit] Lipo-lymphedema, a secondary lymphedema, is associated with both lipedema and obesity (which occur together in the majority of cases), most often lipedema stages 2 and 3.[12] #### Dercum's disease[edit] Lipedema / Dercum's disease differentiation – these conditions may co-exist. Dercum's disease is a syndrome of painful growths in subcutaneous fat. Unlike lipedema, which occurs primarily in the trunk and legs, the fatty growths can occur anywhere on the body.[13][14] ## Treatment[edit] A number of treatments may be useful including physiotherapy and light exercise which does not put undue stress on the lymphatic system.[15] The two most common conservative treatments are manual lymph drainage (MLD) where a therapist gently opens lymphatic channels and move the lymphatic fluid using hands-on techniques, and compression garments that keep the fluid at bay and assist the sluggish lymphatic flow. The use of surgical techniques is not universal but research has shown positive results in both short-term and long-term studies.[16][17] regarding lymph-sparing liposuction and lipectomy.[18] The studies of highest quality involve tumescent local anesthesia (TLA), often referred to as simply tumescent liposuction. This can be accomplished via both Suction-Assisted Liposuction (SAL) and Power-Assisted (vibrating) liposuction.[7][19] The treatment of lipedema with tumescent liposuction may require multiple procedures. While many health insurance carriers in the United States do not reimburse for liposuction for lipedema, in 2020 several carriers regard the procedure as reconstructive and medically necessary and do reimburse.[20] Water Assisted Liposuction (WAL) is technically not considered to be tumescent but achieves the same goal as the anesthetic solution is injected as part of the procedure rather than before-hand. Developed by Doctor Ziah Taufig from Germany, it is usually performed under general anesthesia and is also considered to be lymph-sparing and protective of other tissues such blood vessels. [21] ## Prognosis[edit] Complications include a malformed appearance, reduced functionality (mobility and gait), poor Quality of Life (QOL), depression, anxiety, and pain.[2] ## Epidemiology[edit] According to an epidemiologic study by Földi E and Földi M, lipedema affects 11% of the female population, although rates from 6-39% have also been reported.[22] [23] ## History[edit] Lipedema was first identified in the United States, at the Mayo Clinic in 1940.[24][25] Most attribute the original identification of lipedema to EA Hines and LE Wold (1951).[24] In spite of that lipedema is barely known in the United States to physicians or to the patients who have the disease. Lipedema often is confused with obesity or lymphedema, and a significant number of patients currently diagnosed as obese are believed to have lipedema, either instead of or in addition to obesity.[2] ## See also[edit] * Lymphedema * Steatopygia * Adiposis dolorosa * Lipodystrophy ## References[edit] 1. ^ a b c d e f g h i j k l m n o p "Lipedema". rarediseases.info.nih.gov. Retrieved 30 December 2016. 2. ^ a b c d Herbst, Karen L (2012). "Rare adipose disorders (RADs) masquerading as obesity". Acta Pharmacologica Sinica. 33 (2): 155–72. doi:10.1038/aps.2011.153. PMC 4010336. PMID 22301856. 3. ^ Anne Warren Peled, Anne; Kappos, Elisabeth (August 2016). "Lipedema: diagnostic and management challenges". International Journal of Women's Health. 8: 389–395. doi:10.2147/IJWH.S106227. PMC 4986968. PMID 27570465. 4. ^ a b Vignes S. Lipœdème : une entité mal connue [Lipedema: a misdiagnosed entity]. J Mal Vasc. 2012;37(4):213‐218. doi:10.1016/j.jmv.2012.05.002 5. ^ Fat Disorders Research Society Lipedema Description Archived 2015-07-31 at the Wayback Machine 6. ^ Todd, Marie (2010). "Lipoedema: Presentation and management". British Journal of Community Nursing. 15 (4): S10–6. doi:10.12968/bjcn.2010.15.Sup3.47363. PMID 20559170. 7. ^ a b Fife, Caroline E.; Maus, Erik A.; Carter, Marissa J. (2010). "Lipedema". Advances in Skin & Wound Care. 23 (2): 81–92. doi:10.1097/01.ASW.0000363503.92360.91. PMID 20087075. 8. ^ Földi, Michael; Földi, Ethel, eds. (2006). "Lipedema". Földi's Textbook of Lymphology. Munich: Elsevier. pp. 417–27. ISBN 978-0-7234-3446-7. 9. ^ a b Trayes, K. P.; Studdiford, J. S.; Pickle, S; Tully, A. S. (2013). "Edema: Diagnosis and management". American Family Physician. 88 (2): 102–10. PMID 23939641. 10. ^ Leopoldo Cobos, MD, Karen Herbst, PhD, MD, Christopher Ussery, MS, CSCS, MON-116 Liposuction for Lipedema (Persistent Fat) in the US Improves Quality of Life, Journal of the Endocrine Society, Volume 3, Issue Supplement_1, April-May 2019, MON–116 11. ^ Schmeller W, Hueppe M, Meier-Vollrath I. Tumescent liposuction in lipoedema yields good long-term results. Br J Dermatol. 2012;166(1):161‐168. doi:10.1111/j.1365-2133.2011.10566.x 12. ^ Leopoldo Cobos, MD, Karen Herbst, PhD, MD, Christopher Ussery, MS, CSCS, MON-116 Liposuction for Lipedema (Persistent Fat) in the US Improves Quality of Life, Journal of the Endocrine Society, Volume 3, Issue Supplement_1, April-May 2019, MON–116 13. ^ Beltran K, Herbst KL. Differentiating lipedema and Dercum's disease. Int J Obes (Lond). 2017;41(2):240‐245. doi:10.1038/ijo.2016.205 14. ^ http://fatdisorders.org/fat-disorders/diagram[full citation needed] 15. ^ Fetzer A, Wise C. Living with lipoedema: reviewing different self-management techniques. Br J Community Nurs. 2015;Suppl Chronic:S14‐S19. doi:10.12968/bjcn.2015.20.Sup10.S14 16. ^ Dadras, Mehran; Mallinger, Peter Joachim; Corterier, Cord Christian; Theodosiadi, Sotiria; Ghods, Mojtaba (2017). "Liposuction in the Treatment of Lipedema: A Longitudinal Study". Archives of Plastic Surgery. 44 (4): 324–331. doi:10.5999/aps.2017.44.4.324. PMC 5533060. PMID 28728329. 17. ^ Baumgartner, A.; Hueppe, M.; Schmeller, W. (May 2016). "Long-term benefit of liposuction in patients with lipoedema: a follow-up study after an average of 4 and 8 years". British Journal of Dermatology. 174 (5): 1061–1067. doi:10.1111/bjd.14289. PMID 26574236. 18. ^ Sandhofer M, Hanke CW, Habbema L, et al. Prevention of Progression of Lipedema With Liposuction Using Tumescent Local Anesthesia: Results of an International Consensus Conference. Dermatol Surg. 2020;46(2):220‐228. doi:10.1097/DSS.0000000000002019 19. ^ Langendoen, S.I.; Habbema, L.; Nijsten, T.E.C.; Neumann, H.A.M. (2009). "Lipoedema: From clinical presentation to therapy. A review of the literature". British Journal of Dermatology. 161 (5): 980–6. doi:10.1111/j.1365-2133.2009.09413.x. PMID 19785610. 20. ^ "Cosmetic and Reconstructive Services of the Trunk and Groin". November 12, 2019. 21. ^ Forner-Cordero, I.; Szolnoky, G.; Forner-Cordero, A.; Kemény, L. (2012). "Lipedema: An overview of its clinical manifestations, diagnosis and treatment of the disproportional fatty deposition syndrome - systematic review". Clinical Obesity. 2 (3–4): 86–95. doi:10.1111/j.1758-8111.2012.00045.x. PMID 25586162. 22. ^ Foldi, E. and Foldi, M. (2006) Lipedema. In Foldi's Textbook of Lymphology (Foldi, M., and Foldi, E., eds) pp. 417-427, Elsevier GmbH, Munich, Germany 23. ^ Reich-Schupke S, Schmeller W, Brauer WJ, et al. S1 guidelines: Lipedema. J Dtsch Dermatol Ges. 2017;15(7):758-767. doi: 710.1111/ddg.13036 24. ^ a b Wold, LE; Hines, EA; Allen, EV (1 May 1951). "Lipedema of the legs: a syndrome characterized by fat legs and edema". Annals of Internal Medicine. 34 (5): 1243–50. doi:10.7326/0003-4819-34-5-1243. PMID 14830102. 25. ^ HINES, EA (2 January 1952). "Lipedema and physiologic edema". Proceedings of the Staff Meetings. Mayo Clinic. 27 (1): 7–9. PMID 14900206. ## External links[edit] Classification D * ICD-10: R60, E88.2 * OMIM: 614103 * MeSH: D065134 * DiseasesDB: 7491 External resources * Orphanet: 77243 * v * t * e Medicine Specialties and subspecialties Surgery * Cardiac surgery * Cardiothoracic surgery * Colorectal surgery * Eye surgery * General surgery * Neurosurgery * Oral and maxillofacial surgery * Orthopedic surgery * Hand surgery * Otolaryngology * ENT * Pediatric surgery * Plastic surgery * Reproductive surgery * Surgical oncology * Transplant surgery * Trauma surgery * Urology * Andrology * Vascular surgery Internal medicine * Allergy / Immunology * Angiology * Cardiology * Endocrinology * Gastroenterology * Hepatology * Geriatrics * Hematology * Hospital medicine * Infectious disease * Nephrology * Oncology * Pulmonology * Rheumatology Obstetrics and gynaecology * Gynaecology * Gynecologic oncology * Maternal–fetal medicine * Obstetrics * Reproductive endocrinology and infertility * Urogynecology Diagnostic * Radiology * Interventional radiology * Nuclear medicine * Pathology * Anatomical * Clinical pathology * Clinical chemistry * Cytopathology * Medical microbiology * Transfusion medicine Other * Addiction medicine * Adolescent medicine * Anesthesiology * Dermatology * Disaster medicine * Diving medicine * Emergency medicine * Mass gathering medicine * Family medicine * General practice * Hospital medicine * Intensive care medicine * Medical genetics * Narcology * Neurology * Clinical neurophysiology * Occupational medicine * Ophthalmology * Oral medicine * Pain management * Palliative care * Pediatrics * Neonatology * Physical medicine and rehabilitation * PM&R * Preventive medicine * Psychiatry * Addiction psychiatry * Radiation oncology * Reproductive medicine * Sexual medicine * Sleep medicine * Sports medicine * Transplantation medicine * Tropical medicine * Travel medicine * Venereology Medical education * Medical school * Bachelor of Medicine, Bachelor of Surgery * Bachelor of Medical Sciences * Master of Medicine * Master of Surgery * Doctor of Medicine * Doctor of Osteopathic Medicine * MD–PhD Related topics * Alternative medicine * Allied health * Dentistry * Podiatry * Pharmacy * Physiotherapy * Molecular oncology * Nanomedicine * Personalized medicine * Public health * Rural health * Therapy * Traditional medicine * Veterinary medicine * Physician * Chief physician * History of medicine * Book * Category * Commons * Wikiproject * Portal * Outline [v]: View this template [t]: Discuss this template [e]: Edit this template [c.]: circa [AA]: Adrenergic agonist [AD]: Acetaldehyde dehydrogenase [HAART]: highly active antiretroviral therapy [Ki]: Inhibitor constant [nM]: nanomolars [MOR]: μ-opioid receptor [DOR]: δ-opioid receptor [KOR]: κ-opioid receptor [SERT]: Serotonin transporter [NET]: Norepinephrine transporter [NMDAR]: N-Methyl-D-aspartate receptor [M:D:K]: μ-receptor:δ-receptor:κ-receptor [ND]: No data [NOP]: Nociceptin receptor [BMI]: body mass index [OCD]: Obsessive-compulsive disorder [SSRIs]: Selective serotonin reuptake inhibitors [SNRIs]: Serotonin–norepinephrine reuptake inhibitors [TCAs]: Tricyclic antidepressants [MAOIs]: Monoamine oxidase inhibitors [MSNs]: medium spiny neurons [CREB]: cAMP response element-binding protein [NC]: neurogenic claudication [LSS]: lumbar spinal stenosis [DDD]: degenerative disc disease [CI]: confidence interval [E2]: estradiol [CEEs]: conjugated estrogens	Lipedema	c0398370	3,999	wikipedia	https://en.wikipedia.org/wiki/Lipedema	2021-01-18T18:49:05	{"gard": ["10542"], "mesh": ["D065134"], "umls": ["C0398370"], "orphanet": ["77243"], "wikidata": ["Q1827605"]}

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