Those with this genetic defect develop breasts but do not have their period. Mayer–Rokitansky–Küster–Hauser syndrome is a related but distinct syndrome. Some women who have an initial diagnosis of MRKH have later been found to have WNT4 deficiency. Most women with MRKH syndrome do not have genetic mutations of the WNT4 gene. ... One other rare disorder is known as Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. It is said that women who have WNT4 deficiency have been misdiagnosed with MRKH syndrome due to very similar signs and symptoms, however, the main difference is that in MRKH syndrome, there is no mutation present on the WNT4 gene even though there is an underdevelopment of the uterus/vagina and amenorrhea while still maintaining normal ovarian function. [3] MRKH syndrome is typically the first diagnosis given, but upon extensive genetic testing and imaging analysis, WNT4 deficiency is the correct diagnosis. Additionally, complete androgen insensitivity syndrome is a rare disorder in which individuals are genetically male (46, XY) but they do not respond to androgens . ... "WNT4 deficiency--a clinical phenotype distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome: a case report" . Human Reproduction (Oxford, England) . 22 (1): 224–229. doi : 10.1093/humrep/del360 .
A rare syndrome with 46,XX disorder of sex development characterized by Müllerian duct hypoplasia or agenesis associated with clinical and biological evidence of hyperandrogenism in 46,XX females.
Müllerian aplasia and hyperandrogenism is a condition that affects the reproductive system in females. This condition is caused by abnormal development of the Müllerian ducts, which are structures in the embryo that develop into the uterus, fallopian tubes, cervix, and the upper part of the vagina. Individuals with Müllerian aplasia and hyperandrogenism typically have an underdeveloped or absent uterus and may also have abnormalities of other reproductive organs. Women with this condition have normal female external genitalia, and they develop breasts and pubic hair normally at puberty; however, they do not begin menstruation by age 16 (primary amenorrhea) and will likely never have a menstrual period. Affected women are unable to have children (infertile). Women with Müllerian aplasia and hyperandrogenism have higher-than-normal levels of male sex hormones called androgens in their blood (hyperandrogenism), which can cause acne and excessive facial hair (facial hirsutism).
The authors noted that this phenotype resembled that of patients with the Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH syndrome; 277000), and was strikingly similar to that of Wnt4 (603490)-knockout female mice.
A number sign (#) is used with this entry because of evidence that mitochondrial DNA depletion syndrome-17 (MTDPS17) is caused by homozygous mutation in the MRM2 gene (606906) on chromosome 7p22.
The family had no clinical evidence of connective tissue abnormalities indicative of Stickler syndrome (108300) or Marfan syndrome (154700), both of which have myopia as a feature. ... Young et al. (1998) suggested that fibrillogenesis of the sclera may be affected by mutations in these candidate proteins, as has been demonstrated in connective tissue disorders such as Stickler syndrome and Marfan syndrome. Lin et al. (2010) analyzed 4 promoter SNPs (601T-C, -59CC/-, -628delA, -1554T-C) of the LUM gene for association with high myopia, defined as -6.5 diopters, in 182 affected Taiwanese Chinese individuals and 78 Taiwanese Chinese controls.
Differential diagnosis The relationship of HUV to systemic lupus erythematosus (SLE) is complex with many overlapping features (manifestations of HUV are present in 10% of SLE patients and 50% of patients with HUV will later be diagnosed as having SLE). Other syndromes such as mixed cryoglobulinemia, Muckle-Wells syndrome, Cogan syndrome and Schnitzler syndrome should be excluded (see these terms).
Some scientists refer to the condition as HUV syndrome (HUVS) when it is more severe and there is significant systemic involvement. ... In some cases HUV may be associated with an underlying infection or systemic diseases such as systemic lupus , Sjögren's syndrome , monoclonal gammopathy , or blood disorders.
Differential diagnosis Differential diagnoses include Zollinger-Ellison syndrome (see this term), hypertrophic hypersecretory gastropathy, hypertrophic lymphocytic gastritis, infiltrating neoplasm, polyps, and polyposis syndromes (e.g. juvenile polyposis syndrome, Peutz-Jeghers syndrome, and gastric adenocarcinoma and proximal polyposis of the stomach; see these terms).
Ménétrier disease is a gastrointestinal condition characterized by overgrowth of the mucous cells (foveola) in the mucous membrane lining the stomach, causing enlarged gastric folds. This leads to excessive mucus production, causing protein loss from the stomach and low or absent levels of stomach acid. Symptoms may include pain in the upper middle region of the stomach, nausea, vomiting, and diarrhea. The cause of Ménétrier disease is largely not known, although some cases are associated with infection, particularly pediatric cases, which can be caused by CMV infections . Treatment may include medications such as cetuximab and gastrectomy in severe cases.
Animal Model Slappendel et al. (1994) described an autosomal recessive syndrome in dogs in which hypertrophic gastritis resembling Menetrier disease in man was associated with stomatocytosis (cup- or bowl-shaped red blood cells).
It is also known as cheimaphobia or cheimatophobia . [ citation needed ] Society and culture [ edit ] China [ edit ] In China, frigophobia is known as weihanzheng (畏寒症, lit. "coldness-fearing syndrome"). [ citation needed ] From the standpoint of traditional Chinese beliefs, the disorder is highly influenced by an imbalance of yin (the female element) and yang (the male element). ... See also [ edit ] Culture-bound syndrome Fan death Genital retraction syndrome Traditional Chinese medicine Yin and yang References [ edit ] ^ Kleinman, A.; Lin, T.Y. (1981). ... Wei han zheng (frigophobia): a culture-related psychiatric syndrome. The Australian and New Zealand Journal of Psychiatry [1998, 32(4):582-585]. doi : 10.3109/00048679809068335 Further reading [ edit ] Chang YH, Rin H, Chen CC Frigophobia: a report of five cases.
Differential diagnosis The differential diagnosis of a fulminant MH crisis includes sporadic pheochromocytoma, serotonin syndrome, neuroleptic malignant syndrome (see these terms), anaphylactic reaction, thyroid crisis and sepsis. ... Cooling (with cold intravenous fluids, topical ice or special cooling blankets) is essential as high temperatures exacerbate an established MH reaction. Prognosis The syndrome is likely to be fatal if untreated but thanks to the dramatic progress in understanding the clinical manifestations and pathophysiology of the syndrome, the mortality from MH has dropped from over 80%, thirty years ago, to less than 5% at present.
Skin temperature measurement is often misleading during MH crises [Larach et al 2010]. Acidosis may be mild if the syndrome is recognized and treated promptly. ... Hyperkalemia, leading to cardiac arrhythmia and even arrest, is uncommon if the syndrome is detected and treated promptly but may develop with remarkable rapidity. ... However, a completely normal response to succinylcholine may be present in some individuals susceptible to MH; in these individuals, a potent inhalation agent is apparently necessary to trigger the syndrome. In almost all instances, the first manifestations of MH occur in the operating room. ... Even with treatment and survival, the individual is at risk for life-threatening myoglobinuric renal failure, disseminated intravascular coagulation (DIC), compartment syndrome, and recrudescence of the syndrome within the first 24-36 hours following the episode. ... Pathogenic variants in RYR1 have been found in some individuals with King-Denborough syndrome. STAC3 disorder (Native American myopathy), caused by biallelic pathogenic variants in STAC3 , is characterized by congenital myopathy and musculoskeletal involvement of the trunk and extremities.
For a phenotypic description and a discussion of genetic heterogeneity of malignant hyperthermia, see MHS1 (145600). Mapping In a single German pedigree with classic malignant hyperthermia, Sudbrak et al. (1995) found a maximum multipoint lod score of 3.22 for linkage to markers defining a 1-cM interval on 3q13.1. The malignant hyperthermia phenotype was determined by the in vitro contracture test (IVCT) performed on a sample of freshly obtained muscle. Muscle - Masseter or generalized muscle contracture - Rhabdomyolysis Misc - Triggered by certain anesthetics, such as halothane or succinylcholine - Rapid body temperature rise Inheritance - Autosomal dominant (3q13.1) Metabolic - Malignant hyperthermia - Acidosis - Hypoxia ▲ Close
Malignant hyperthermia (MH) is a severe reaction to certain gases used during anesthesia and/or a muscle relaxant used to temporarily paralyze a person during surgery. Signs and symptoms of MH include marked hyperthermia, a rapid heart rate, rapid breathing, acidosis, muscle rigidity, and breakdown of muscle tissue (rhabdomyolysis). Without prompt treatment, MH can be life-threatening. People who are at increased risk for this reaction are said to have MH susceptibility. Susceptibility to MH may be caused by mutations in any of several genes and is inherited in an autosomal dominant manner. People with certain inherited muscle diseases (e.g., central core disease and multiminicore disease ) also have MH susceptibility.
As these channels interact with and activate RYR1, these alterations result in a drastic increase of intracellular Ca 2+ , and, thereby, muscle excitability. [16] Other mutations causing MH have been identified, although in most cases the relevant gene remains to be identified. [17] Animal model [ edit ] Research into malignant hyperthermia was limited until the discovery of " porcine stress syndrome " (PSS) in Danish Landrace and other pig breeds selected for muscling, a condition in which stressed pigs develop "pale, soft, exudative" flesh (a manifestation of the effects of malignant hyperthermia) rendering their meat less marketable at slaughter. ... "Exertional rhabdomyolysis in quarter horses and thoroughbreds: one syndrome, multiple aetiologies" . Equine Veterinary Journal. ... "Control of the malignant hyperpyrexic syndrome in MHS swine by dantrolene sodium" . ... "Control of the malignant hyperpyrexic syndrome in MHS swine by dantrolene sodium. 1975". ... External links [ edit ] GeneReview/NIH/UW entry on Malignant Hyperthermia Susceptibility Classification D ICD - 10 : T88.3 ICD - 9-CM : 995.86 OMIM : 145600 MeSH : D008305 DiseasesDB : 7776 External resources MedlinePlus : 001315 GeneReviews : Malignant Hyperthermia Susceptibility v t e Diseases of ion channels Calcium channel Voltage-gated CACNA1A Familial hemiplegic migraine 1 Episodic ataxia 2 Spinocerebellar ataxia type-6 CACNA1C Timothy syndrome Brugada syndrome 3 Long QT syndrome 8 CACNA1F Ocular albinism 2 CSNB2A CACNA1S Hypokalemic periodic paralysis 1 Thyrotoxic periodic paralysis 1 CACNB2 Brugada syndrome 4 Ligand gated RYR1 Malignant hyperthermia Central core disease RYR2 CPVT1 ARVD2 Sodium channel Voltage-gated SCN1A Familial hemiplegic migraine 3 GEFS+ 2 Febrile seizure 3A SCN1B Brugada syndrome 6 GEFS+ 1 SCN4A Hypokalemic periodic paralysis 2 Hyperkalemic periodic paralysis Paramyotonia congenita Potassium-aggravated myotonia SCN4B Long QT syndrome 10 SCN5A Brugada syndrome 1 Long QT syndrome 3 SCN9A Erythromelalgia Febrile seizure 3B Paroxysmal extreme pain disorder Congenital insensitivity to pain Constitutively active SCNN1B / SCNN1G Liddle's syndrome SCNN1A / SCNN1B / SCNN1G Pseudohypoaldosteronism 1AR Potassium channel Voltage-gated KCNA1 Episodic ataxia 1 KCNA5 Familial atrial fibrillation 7 KCNC3 Spinocerebellar ataxia type-13 KCNE1 Jervell and Lange-Nielsen syndrome Long QT syndrome 5 KCNE2 Long QT syndrome 6 KCNE3 Brugada syndrome 5 KCNH2 Short QT syndrome KCNQ1 Jervell and Lange-Nielsen syndrome Romano–Ward syndrome Short QT syndrome Long QT syndrome 1 Familial atrial fibrillation 3 KCNQ2 BFNS1 Inward-rectifier KCNJ1 Bartter syndrome 2 KCNJ2 Andersen–Tawil syndrome Long QT syndrome 7 Short QT syndrome KCNJ11 TNDM3 KCNJ18 Thyrotoxic periodic paralysis 2 Chloride channel CFTR Cystic fibrosis Congenital absence of the vas deferens CLCN1 Thomsen disease Myotonia congenita CLCN5 Dent's disease CLCN7 Osteopetrosis A2, B4 BEST1 Vitelliform macular dystrophy CLCNKB Bartter syndrome 3 TRP channel TRPC6 FSGS2 TRPML1 Mucolipidosis type IV Connexin GJA1 Oculodentodigital dysplasia Hallermann–Streiff syndrome Hypoplastic left heart syndrome GJB1 Charcot–Marie–Tooth disease X1 GJB2 Keratitis–ichthyosis–deafness syndrome Ichthyosis hystrix Bart–Pumphrey syndrome Vohwinkel syndrome ) GJB3 / GJB4 Erythrokeratodermia variabilis Progressive symmetric erythrokeratodermia GJB6 Clouston's hidrotic ectodermal dysplasia Porin AQP2 Nephrogenic diabetes insipidus 2 See also: ion channels v t e Anesthesia and anesthesiology Types General Sedation Twilight anesthesia Local Topical Intercostal nerve block Neuraxial blockade Spinal Epidural Dental Inferior alveolar nerve Techniques Airway management Anesthesia provision in the US Arterial catheter Bronchoscopy Capnography Dogliotti's principle Drug-induced amnesia Intraoperative neurophysiological monitoring Nerve block Penthrox inhaler Tracheal intubation Scientific principles Blood–gas partition coefficient Concentration effect Fink effect Minimum alveolar concentration Second gas effect Measurements ASA physical status classification system Baricity Bispectral index Entropy monitoring Fick principle Goldman index Guedel's classification Mallampati score Neuromuscular monitoring Thyromental distance Instruments Anaesthetic machine Anesthesia cart Boyle's machine Gas cylinder Laryngeal mask airway Laryngeal tube Medical monitor Odom's indicator Relative analgesia machine Vaporiser Double-lumen endotracheal tube Endobronchial blocker Complications Emergence delirium Allergic reactions Anesthesia awareness Local anesthetic toxicity Malignant hyperthermia Perioperative mortality Postanesthetic shivering Postoperative nausea and vomiting Postoperative residual curarization Subspecialties Cardiothoracic Critical emergency medicine Geriatric Intensive care medicine Obstetric Oral sedation dentistry Pain medicine Professions Anesthesiologist Anesthesiologist assistant Nurse anesthetist Operating department practitioners Certified Anesthesia Technician Certified Anesthesia Technologist Anaesthetic technician Physicians' assistant (anaesthesia) History ACE mixture Helsinki Declaration for Patient Safety in Anaesthesiology History of general anesthesia History of neuraxial anesthesia History of tracheal intubation Organizations American Association of Nurse Anesthetists American Society of Anesthesia Technologists & Technicians American Society of Anesthesiologists Anaesthesia Trauma and Critical Care Association of Anaesthetists of Great Britain and Ireland Royal College of Anaesthetists Association of Veterinary Anaesthetists Australian and New Zealand College of Anaesthetists Australian Society of Anaesthetists International Anesthesia Research Society Category Outline
For a phenotypic description and a discussion of genetic heterogeneity of malignant hyperthermia, see MHS1 (145600). By linkage studies in 3 families, Sudbrak et al. (1993) excluded linkage either to chromosome 19 or 17q, thus suggesting the existence of a third locus for malignant hyperthermia susceptibility. In MHS families linked to neither chromosome 17 nor chromosome 19, Iles et al. (1994) found linkage with no recombination to markers flanking the CACNA2D1 gene (114204) on chromosome 7. Since this gene encodes a subunit of the L-type voltage-dependent calcium channel that is intimately associated at the skeletal muscle triadic junctions with the ryanodine receptor (RYR1; 180901), it is possible that the mutation is located in this gene. In affected members of a family linked to the MHS3 locus by Iles et al. (1994), Schleithoff et al. (1999) did not identify any pathogenic mutations in the coding region of the CACNA2D1 gene.
Overview Malignant hyperthermia is a severe reaction to certain drugs used for anesthesia. This severe reaction typically includes a dangerously high body temperature, rigid muscles or spasms, a rapid heart rate, and other symptoms. Without prompt treatment, the complications caused by malignant hyperthermia can be fatal. In most cases, the gene that puts you at risk of malignant hyperthermia is inherited, though sometimes it's the result of a random genetic change. Genetic testing can reveal whether you have an affected gene. This genetic disorder is called malignant hyperthermia susceptibility (MHS).
For a phenotypic description and a discussion of genetic heterogeneity of malignant hyperthermia, see MHS1 (145600). Mapping In a Belgian kindred with malignant hyperthermia, Robinson et al. (1997) performed a genomewide search for the locus responsible for this disorder. Disease status was classified according to the European IVCT (in vitro contracture tests) protocol. Multipoint linkage analysis showed linkage to the region on 5p between D5S419 and D5S398. They also found linkage of MHS to chromosome 1q (601887). Robinson et al. (1997) stated that studies in a third kindred suggested the existence of at least 1 more MHS locus.
For a phenotypic description and a discussion of genetic heterogeneity of malignant hyperthermia, see MHS1 (145600). Mapping In 3 unrelated families, Levitt et al. (1991) excluded linkage of the MHS phenotype to loci on 19q13.1, thus indicating genetic heterogeneity. Levitt et al. (1992) extended these studies to 16 MHS families. Four were found to be linked to chromosome 19; 5 were found to be closely linked to the anonymous marker NM23 (156490) on 17q11.2-q24 (maximum lod = 3.26 at theta = 0.0); and 2 families were clearly unlinked to either of these regions. In 5 additional families, there were insufficient data to determine their linkage status. Olckers et al. (1992) provided evidence for linkage of MHS to the SCN4A gene (603967), which encodes the adult sodium channel alpha subunit, in 3 informative families (cumulative lod score of 2.1 at theta = 0.0).
A number sign (#) is used with this entry because susceptibility to malignant hyperthermia-5 (MHS5) is caused by heterozygous mutation in the CACNA1S gene (114208) on chromosome 1q32. For a phenotypic description and a discussion of genetic heterogeneity of malignant hyperthermia, see MHS1 (145600). Mapping In a collaborative study in 3 pedigrees in Europe, in which disease status was classified according to the European in vitro contracture test (IVCT), Robinson et al. (1997) performed a genomewide screen and found that at least 2 further loci exist for MH susceptibility. One of these was located on 5p (601888). The other was located on 1q, between markers D1S422 and D1S1660. Between these 2 markers had already been localized a candidate gene, CACNL1A3 (CACNA1S; 114208), assigned to 1q32.
Malignant hyperthermia is a severe reaction to particular anesthetic drugs that are often used during surgery and other invasive procedures. Specifically, this reaction occurs in response to some anesthetic gases, which are used to block the sensation of pain, either given alone or in combination with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk of malignant hyperthermia may experience a rapid increase in heart rate and body temperature (hyperthermia), abnormally fast breathing, muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), and increased acid levels in the blood and other tissues (acidosis). Without prompt treatment and cessation of the drugs, the body's reaction can cause multiple organs to be unable to function, including the heart (cardiac arrest) and kidneys (renal failure), and it can cause a blood clotting abnormality called disseminated intravascular coagulation. These complications may be life-threatening. (In medicine, the term malignant refers to conditions that are dangerous to one's health.)