{"id":990,"date":"2023-08-17T21:48:43","date_gmt":"2023-08-17T19:48:43","guid":{"rendered":"https:\/\/neurokidbossa.rs\/?p=990"},"modified":"2023-08-17T23:44:49","modified_gmt":"2023-08-17T21:44:49","slug":"joubert-syndrome","status":"publish","type":"post","link":"https:\/\/neurokidbossa.rs\/en\/joubert-syndrome\/","title":{"rendered":"Joubert syndrome (JS)"},"content":{"rendered":"<h2 class=\"wp-block-heading\"><\/h2>\n\n\n\n<p>As several patients in our outpatient clinic had genetically confirmed Joubert syndrome, we thought it would be interesting to describe this syndrome in more detail.<\/p>\n\n\n\n<p>Joubert syndrome is a rare genetic disease characterized by irregular development of certain parts of the brain, characterized by problems in intellectual and motor development, kidney and liver function, as well as eye disorders.<\/p>\n\n\n\n<p>It is inherited in an autosomal recessive manner and mostly affects the brain structures responsible for balance and coordination, which we call the cerebellum. For this reason, the most striking symptoms are hypotonia, lack of muscle control - ataxia, breathing problems (Hyperpnea), sleep apnea, abnormal eye movements and the inability to move the eyeballs in all directions (oculomotor dyspraxia), epileptic seizures.<\/p>\n\n\n\n<p>Joubert syndrome was first described by Dr. Marie Joubert, a child neurologist in 1969. when she and her colleagues described 4 family members who had an underdeveloped cerebellar vermis - the part that connects the two cerebellar hemispheres (vermis) and had symptoms of increased respiration (hyperpnea), abnormal eye movements, ataxia and intellectual disability. A few years later, with the development of neuroimaging techniques, a specific neuroradiological finding was found - the \"molar sign\" which became an important diagnostic criterion for the diagnosis of JS.<\/p>\n\n\n\n<p>Given that it affects several organs (eyes, liver, kidney, brain, skeleton), it belongs to multiorgan disorders. Other eye problems that can be found in Joubert syndrome include: retinal abnormalities, eye twitching (nystagmus), wide-eyed vision (strabismus), iris disorder (coloboma), or eyelid droop (ptosis). There can also be associated disorders of the skeletal system in the form of the 6th finger (polydactyly) both on the legs and on the hands, hormonal disorders, cleft soft palate, tongue malformations, corticomedullary kidney cysts, polycystic kidneys, and liver fibrosis as well as a disorder at the level of the meninges in such as encephalocele, as well as epileptic seizures.<\/p>\n\n\n\n<p>On magnetic resonance imaging of the brain (MRI brain), which is very important for the neuroimaging diagnosis of Joubert syndrome, there is a typical molar tooth sign characterized by the absence or insufficiently developed cerebellar vermis and brainstem abnormalities.<\/p>\n\n\n\n<p>Since then, with the development of genetics, more than 35 genes have been found that are responsible for the clinical manifestation of Joubert syndrome. Molecular diagnosis of JS can be established in 60-90% of cases.<\/p>\n\n\n\n<p>The clinical presentation of Joubert syndrome also depends on the affected gene. Mutation <em>AHI1&nbsp;<\/em>(<em>JBTS3<\/em>) gena javlja se u oko ~7%-10% porodica. Obolele osobe sa ovom mutacijom imaju problem sa vidom zbog retinalne distrofije. Mutacija <em>NPHP1&nbsp;<\/em>(<em>JBTS4<\/em>) gena uzrokuje oko 1-2% JS. Osobe sa ovom mutacijom imaju progresivnu bubre\u017enu boest. Mutacija <em>CEP290&nbsp;<\/em>(<em>JBTS5<\/em>) gene is responsible for about 7-10% of JS. Gene mutations <em>CPLANE1<\/em>,&nbsp;<em>CC2D2A<\/em>,&nbsp;<em>INPP5E<\/em>,&nbsp;<em>KIAA0586<\/em>,&nbsp;<em>MKS1<\/em>,&nbsp;<em>RPGRIP1L TCTN2<\/em>,&nbsp;<em>TMEM67&nbsp;<\/em>and&nbsp;<em>TMEM216&nbsp;<\/em>are less common but are also responsible for JS.<\/p>\n\n\n\n<p>Rare cases of JS are caused by a mutation <em>OFD1&nbsp;<\/em>gene that is inherited recessively linked to the X chromosome and most often occurs in males. Females who carry the mutation are only carriers of the pathological gene (Carrier) and do not show clinical symptoms because they have two X chromosomes, while boys have only 1, so the manifestation of the disease related to the X chromosome is inevitable.<\/p>\n\n\n\n<p><strong>Diagnostics and follow-up of patients with JS<\/strong><\/p>\n\n\n\n<p>We have already mentioned that JS is a multisystem disease, and accordingly, diagnosis and follow-up includes the neurological, genetic and pediatric areas.<\/p>\n\n\n\n<p>Therefore, for the diagnosis and further follow-up of people with JB, it is necessary:<\/p>\n\n\n\n<ol class=\"wp-block-list\" type=\"1\">\n<li>Neuroradiological examination - MRI of the brain to detect brain malformations (\"molar tooth sign\")<\/li>\n\n\n\n<li>Basic neurological examination of tone, motor skills, eye movements, respiration and psychomotor development<\/li>\n\n\n\n<li>EEG if the JS patient has epileptic seizures<\/li>\n\n\n\n<li>Ophthalmologist consultation for eye abnormalities (retinal dystrophy, strabismus and coloboma)<\/li>\n\n\n\n<li>Ultrasound examination of the abdomen (monitoring of liver and kidney function)<\/li>\n\n\n\n<li>Laboratory tests including blood count, renal and liver function, urea and creatinine, urine analysis<\/li>\n\n\n\n<li>X-ray of hands and feet in case of extra finger or toe<\/li>\n\n\n\n<li>Consultation of a geneticist for a possible genetic test and genetic counseling<\/li>\n<\/ol>\n\n\n\n<p><strong>Treatment of JS<\/strong><\/p>\n\n\n\n<p>Treatment of JS is usually symptomatic and suppurative. Slowed psychomotor development requires an intensive program of psychomotor reeducation with a team of experts such as a speech therapist, a speech therapist, a speech therapist, a physiotherapist, occupational therapy, and a nutritionist.<\/p>\n\n\n\n<p>A multidisciplinary approach is necessary including the following types of specialties: pediatric neurologist, physiatrist, ophthalmologist, pediatric nephrologist and gastroenterologist, geneticist. Monitoring of kidney and liver function should be done on an annual basis.<\/p>\n\n\n\n<p>The role of the neurologist is particularly important in cases of JS who have epileptic seizures.<\/p>\n\n\n\n<p>Read more about epileptic seizures here: <a href=\"https:\/\/neurokidbossa.rs\/en\/tipovi-epilepticnih-napada\/\">Types of Epileptic Seizures - Neuro Kid Bossa<\/a><\/p>\n\n\n\n<p>There is an association of patients with JS and their families that started working in 1992 and you can find details about their work and struggle on the website: https:\/\/jsrdf.org\/<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><img fetchpriority=\"high\" decoding=\"async\" width=\"630\" height=\"630\" src=\"https:\/\/neurokidbossa.rs\/wp-content\/uploads\/2023\/08\/kk.jpg\" alt=\"\" class=\"wp-image-991\" srcset=\"https:\/\/neurokidbossa.rs\/wp-content\/uploads\/2023\/08\/kk.jpg 630w, https:\/\/neurokidbossa.rs\/wp-content\/uploads\/2023\/08\/kk-300x300.jpg 300w, https:\/\/neurokidbossa.rs\/wp-content\/uploads\/2023\/08\/kk-150x150.jpg 150w\" sizes=\"(max-width: 630px) 100vw, 630px\" \/><\/figure>\n\n\n\n<p>Characteristic molar tooth sign on brain MRI (tooth-molar appearance)    <br>.<\/p>\n\n\n\n<p>     <\/p>\n\n\n\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34846692\/\" target=\"_blank\" rel=\"noreferrer noopener\">Get Your Molar Tooth Right:\u00a0Joubert\u00a0Syndrome Misdiagnosis Unmasked by Whole-Exome Sequencing.<\/a><\/p>\n\n\n\n<p>D&#8217;Abrusco&nbsp;F,&nbsp;Arrigoni&nbsp;F,&nbsp;Serpieri&nbsp;V,&nbsp;Romaniello&nbsp;R,&nbsp;Caputi&nbsp;C, Manti F,&nbsp;<strong>Jocic-Jakubi B<\/strong>,&nbsp;Lucarelli&nbsp;E,&nbsp;Panzeri&nbsp;E,&nbsp;Bonaglia&nbsp;MC,&nbsp;Chiapparini&nbsp;L,&nbsp;Pichiecchio&nbsp;A,&nbsp;Pinelli&nbsp;L,&nbsp;Righini&nbsp;A,&nbsp;Leuzzi&nbsp;V,&nbsp;Borgatti&nbsp;R, Valente&nbsp;EM.Cerebellum. 2022 Dec;21(6):1144-1150.&nbsp;doi: 10.1007\/s12311-021-01350-8.&nbsp;Epub&nbsp;2021 Nov 30.PMID:&nbsp;34846692<\/p>\n\n\n\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/23386033\/\" target=\"_blank\" rel=\"noreferrer noopener\"><br>Phenotypic spectrum and prevalence of INPP5E mutations in\u00a0Joubert\u00a0syndrome and related disorders.<\/a><\/p>\n\n\n\n<p>Travaglini&nbsp;L,&nbsp;Brancati&nbsp;F,&nbsp;Silhavy&nbsp;J,&nbsp;Iannicelli&nbsp;M, Nickerson E,&nbsp;Elkhartoufi&nbsp;N, Scott E, Spencer E, Gabriel S, Thomas S, Ben-Zeev&nbsp;B,&nbsp;Bertini&nbsp;E,&nbsp;Boltshauser&nbsp;E,&nbsp;Chaouch&nbsp;M,&nbsp;Cilio&nbsp;MR, de Jong MM,&nbsp;Kayserili&nbsp;H,&nbsp;Ogur&nbsp;G, Poretti A,&nbsp;Signorini&nbsp;S,&nbsp;Uziel&nbsp;G,&nbsp;Zaki&nbsp;MS; International JSRD Study Group; Johnson C,&nbsp;Atti\u00e9-Bitach&nbsp;T, Gleeson JG, Valente&nbsp;EM.Eur&nbsp;J Hum Genet. 2013 Oct;21(10):1074-8.&nbsp;doi: 10.1038\/ejhg.2012.305.&nbsp;Epub&nbsp;2013 Feb 6.PMID:&nbsp;23386033&nbsp;<strong>Free PMC article.<\/strong><\/p>\n\n\n\n<p><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/20232449\/\" target=\"_blank\" rel=\"noreferrer noopener\"><br>Novel TMEM67 mutations and genotype-phenotype correlates in&nbsp;meckelin-related ciliopathies.<\/a><\/p>\n\n\n\n<p>Iannicelli&nbsp;M,&nbsp;Brancati&nbsp;F,&nbsp;Mougou-Zerelli&nbsp;S,&nbsp;Mazzotta&nbsp;A, Thomas S,&nbsp;Elkhartoufi&nbsp;N,&nbsp;Travaglini&nbsp;L, Gomes C,&nbsp;ArdissinoGL,&nbsp;Bertini&nbsp;E,&nbsp;Boltshauser&nbsp;E,&nbsp;Castorina&nbsp;P,&nbsp;D&#8217;Arrigo&nbsp;S,&nbsp;FischettoR, Leroy B,&nbsp;Loget&nbsp;P,&nbsp;Bonni\u00e8re&nbsp;M,&nbsp;Starck&nbsp;L,&nbsp;Tantau&nbsp;J,&nbsp;GentilinB,&nbsp;Majore&nbsp;S,&nbsp;Swistun&nbsp;D,&nbsp;Flori&nbsp;E,&nbsp;Lalatta&nbsp;F, Pantaleoni C,&nbsp;Penzien&nbsp;J,&nbsp;Grammatico&nbsp;P; International JSRD Study Group;&nbsp;Dallapiccola&nbsp;B, Gleeson JG,&nbsp;Attie-Bitach&nbsp;T, Valente&nbsp;EM.HumMutat. 2010 May;31(5):E1319-31.&nbsp;doi: 10.1002\/humu.21239.PMID:&nbsp;20232449&nbsp;<strong>Free PMC article.<\/strong><\/p>","protected":false},"excerpt":{"rendered":"<p>Kako nam je u ordinaciji nekoliko pacijenata imalo geneti\u010dki potvr\u0111en Joubert sindrom, smatrali smo da je interesantno opisati sa vi\u0161e detalja ovaj sindrom. Joubert syndrome je retka geneti\u010dka bolest koju karakteri\u0161e nepravilan razvoj pojedinih delova mozga a koji se karakteri\u0161e problemima u intelektualnom i motorickom razvoju , bubre\u017enoj i jetrinoj funkciji kao i o\u010dnim poreme\u0107ajima. [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[1],"tags":[],"class_list":["post-990","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - 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