{"id":314,"date":"2020-10-09T14:47:27","date_gmt":"2020-10-09T05:47:27","guid":{"rendered":"https:\/\/plaza.umin.ac.jp\/tks\/?page_id=314"},"modified":"2020-10-15T11:10:25","modified_gmt":"2020-10-15T02:10:25","slug":"disease","status":"publish","type":"page","link":"https:\/\/plaza.umin.ac.jp\/tks\/en\/disease\/","title":{"rendered":"Disease overview"},"content":{"rendered":"<script>\n  var target = document.getElementById(\"site_name\")\n  target.href = \"https:\/\/plaza.umin.ac.jp\/tks\/en\"\n<\/script>\n<h2>What are CDC42 and Takenouchi-Kosaki syndrome?<\/h2>\n<p>Takenouchi-Kosaki syndrome is a congenital malformation syndrome characterized by macrothrombocytopenia, intellectual disability, characteristic facial features, sensorineural deafness, brain structural abnormalities, contracture of the fingers, lymphedema, repetitive infections, and hypothyroidism. Although many symptoms are present, this condition can be diagnosed clinically based on a combination of symptoms. This condition is caused by an abnormality in a gene called CDC42. On the other hand, not everyone with mutations in the CDC42 gene will have the same symptoms; only those with a mutation in a specific part of the CDC42 gene appear to exhibit the characteristic symptoms described above.<\/p>\n<div class=\"divider_padding\"><\/div>\n<h3>Prevalence<\/h3>\n<div class=\"one_fourth\"><\/div>\n<div class=\"three_fourth last\">The exact prevalence of the disease is unknown, but several patients in Japan and abroad have been documented. Patients who remain undiagnosed are also thought to exist.<\/div><div class=\"clearboth\"><\/div>\n<h3>Cause<\/h3>\n<div class=\"one_fourth\"><\/div>\n<div class=\"three_fourth last\">Takenouchi-Kosaki syndrome is caused by a specific amino acid substitution mutation in the CDC42 gene, which is located on chromosome 1. The syndrome is caused by an alteration in one of the two CDC42 genes (called an autosomal dominant trait). Although previous basic medical research has shown the CDC42 gene to play an important role in cell division and proliferation and more than 5,000 papers have been published on this topic, it wasn\u2019t until 2015 that abnormalities in this gene were shown to be a direct cause of human disease. The mechanisms by which mutations in the CDC42 gene cause the appearance of giant platelets and other symptoms remain unknown but are thought to involve cytoskeletal anomalies. Different types of mutations may cause some differences in symptoms.<\/p><\/div><div class=\"clearboth\"><\/div>\n<h3>Inheritance<\/h3>\n<div class=\"one_fourth\"><\/div>\n<div class=\"three_fourth last\">This disease is an autosomal dominant genetic disorder that can be diagnosed based on a combination of symptoms and that can be confirmed using genetic testing. Genetic counseling is recommended for patients in whom the genetic status is uncertain.<br \/><\/div><div class=\"clearboth\"><\/div>\n<h3>Differential diagnosis<\/h3>\n<div class=\"one_fourth\"><\/div>\n<div class=\"three_fourth last\">Several diseases are characterized by the presence of both thrombocytopenia and intellectual disability. Typical examples are Jacobsen\u2019s syndrome (11q deletion) and 21q22 microdeletion syndrome. These diseases can be differentiated from Takenouchi-Kosaki syndrome based on the presence or absence of other symptoms. Chromosomal and genetic testing may be necessary.<br \/><\/div><div class=\"clearboth\"><\/div>\n<h3>Treatment<\/h3>\n<div class=\"one_fourth\"><\/div>\n<div class=\"three_fourth last\">Currently, no fundamental treatment exists for this disease. Symptomatic treatment can be performed for each symptom.<br \/><\/div><div class=\"clearboth\"><\/div>\n<h3>Symptoms<\/h3>\n<div class=\"one_fourth\"><\/div>\n<div class=\"three_fourth last\">Symptoms that are present in most patients include macrothrombocytopenia, intellectual disability, brain structural abnormalities, characteristic facial features, and sensorineural deafness. In some patients, lymphedema, repetitive infections, and hypothyroidism may also be present.<\/p>\n<p>\n<img src=\"https:\/\/plaza.umin.ac.jp\/tks\/cms\/wp-content\/uploads\/2020\/10\/tks_symptoms_en-1024x576.png\" alt=\"Symptoms\" width=\"1024\" height=\"576\" class=\"aligncenter size-large wp-image-409\" srcset=\"https:\/\/plaza.umin.ac.jp\/tks\/cms\/wp-content\/uploads\/2020\/10\/tks_symptoms_en-1024x576.png 1024w, https:\/\/plaza.umin.ac.jp\/tks\/cms\/wp-content\/uploads\/2020\/10\/tks_symptoms_en-300x169.png 300w, https:\/\/plaza.umin.ac.jp\/tks\/cms\/wp-content\/uploads\/2020\/10\/tks_symptoms_en-768x432.png 768w, https:\/\/plaza.umin.ac.jp\/tks\/cms\/wp-content\/uploads\/2020\/10\/tks_symptoms_en.png 1200w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><br \/>\n<\/p>\n<h4>Macrothrombocytopenia<\/h4>\n<p>Blood test findings that are characteristic of the disease include a decrease in the number of platelets and an increase in the size of some platelets. This can be confirmed by peripheral blood counts and smear tests performed as part of routine clinical practice. This finding is very important in making a diagnosis. In general, a low platelet count can cause bleeding, but patients with this disease do not have bleeding tendency.<\/p>\n<h4>Intellectual disability<\/h4>\n<p>Patients with this condition exhibit intellectual disability of varying degrees. Regression (a gradual loss of ability to do what was previously possible) is not seen.<\/p>\n<h4>Distinctive facial features<\/h4>\n<p>The following facial features are common in patients with Takenouchi-Kosaki syndrome.<\/p>\n<ul>\n<li>Dark eyebrows and slight hypertrichosis throughout<\/li>\n<li>Inverted crescent-shaped eyelids<\/li>\n<li>A short distance between the nose and mouth<\/li>\n<li>Thin upper lip<\/li>\n<li>Small mouth<\/li>\n<li>Protruding lower jaw, relative to the upper jaw<\/li>\n<li>Small earlobes<\/li>\n<\/ul>\n<h4>Structural brain abnormalities<\/h4>\n<p>The CDC42 gene, which is the cause of this disease, is important for brain formation and is associated with findings such as ventricular enlargement and cerebellar hypoplasia. Among the patients observed to date, a susceptibility to epilepsy has not been reported.<\/p>\n<h4>Sensorineural hearing loss<\/h4>\n<p>Patients with Takenouchi-Kosaki syndrome have sensorineural hearing loss to the extent that a hearing aid is required immediately after birth. The hearing loss is thought to be caused by dysplasia of the inner ear.<\/p>\n<h4>Contracture of the fingers<\/h4>\n<p>Flexion of the fingers and toes is present.<\/p>\n<h4>Lymphedema<\/h4>\n<p>\u201cSwelling\u201d occurring mainly in the lower extremities may be present, particularly in adult patien<\/p>\n<h4>Repetitive infections<\/h4>\n<p>Some patients are susceptible to recurring bacterial infections. While the exact cause is unknown, poor immunity is thought to be involved.<\/p>\n<h4>Hypothyroidism<\/h4>\n<p>A blood test may reveal hypothyroidism.<\/p>\n<p><\/div><div class=\"clearboth\"><\/div>\n","protected":false},"excerpt":{"rendered":"<p>What are CDC42 and Takenouchi-Kosaki syndrome? Takenouchi-Kosaki syndrome is a congenital malformation syndrom &#8230;<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":357,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/plaza.umin.ac.jp\/tks\/wp-json\/wp\/v2\/pages\/314"}],"collection":[{"href":"https:\/\/plaza.umin.ac.jp\/tks\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/plaza.umin.ac.jp\/tks\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/plaza.umin.ac.jp\/tks\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/plaza.umin.ac.jp\/tks\/wp-json\/wp\/v2\/comments?post=314"}],"version-history":[{"count":4,"href":"https:\/\/plaza.umin.ac.jp\/tks\/wp-json\/wp\/v2\/pages\/314\/revisions"}],"predecessor-version":[{"id":428,"href":"https:\/\/plaza.umin.ac.jp\/tks\/wp-json\/wp\/v2\/pages\/314\/revisions\/428"}],"up":[{"embeddable":true,"href":"https:\/\/plaza.umin.ac.jp\/tks\/wp-json\/wp\/v2\/pages\/357"}],"wp:attachment":[{"href":"https:\/\/plaza.umin.ac.jp\/tks\/wp-json\/wp\/v2\/media?parent=314"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}