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CLINICAL INSIGHTS INTRODUCTION by Gisele Ishak, M.D VOLUME 5 / NUMBER 1 SPRING 2011 The Official NewsleTTer Of The americaN sOcieTy Of PediaTric NeurOradiOlOgy YRATIONS CLINICAL INSIGHTS INTRODUCTION BY Gisele Ishak, M.D. and Dan DohertY, M.D., Ph.D. Seattle Children’s Hospital and UniVersitY of Washington Welcome to this latest edition of GYrations. Drs. Gisele Ishak and Dan THE MOLAR TOOTH SIGN (MTS): DohertY contribute to the Clinical JOUBERT SYNDROME AND RELATED DISORDERS Insight column an update on the deVel - oping understanding of the so-called the diVerse and oVerlapping clinical features Introduction Molar Tooth Malformation, and the noW In 1969, Marie Joubert et al, first de - seen in patients. Other ciliopathies include termed Joubert SYndrome Related scribed Joubert sYndrome in four siblings polYcYstic kidneY disease, NPH, some forms Disorders. The eVer-increasing under - With cerebellar Vermis agenesis, ataXia, of retinal dYstrophY, as Well as Meckel (MKS), standing of genetic and molecular ele - episodic tachYpnea, abnormal eYe moVe - Bardet-Biedl, Jeune, Alström, Usher and ments of deVelopment demand our ment and intellectual disabilitY. With the ad - Sensenbrenner sYndromes. Genetic and clin - increasing knoWledge of the imaging Vent of cross sectional imaging a ical oVerlap maY be seen: as noted aboVe, phenotYpe-genotYpe correlations. Drs. pathognomonic midbrain-hindbrain mal- JSRD are caused bY >10 different genes, Korgun Koral and Linda Heier pro - formation, the molar tooth sign (MTS), Was While each gene (e.g. CEP290) can cause Vide an article outlining hoW, in their in - described first in Joubert sYndrome and sub - multiple sYndromes (e.g. MKS, JSRD and iso - stitutions, theY haVe altered imaging management of hYdrocephalus to fol - sequentlY in seVeral other conditions. lated retinal dYstrophY). loW the ALARA principles. We hope this RecentlY, the term “Joubert sYndrome and Imaging and pathology: can help further the mission Within the related disorders” (JSRD) has been adopted pediatric World to reduce radiation eX - The essential features of the MTS are to describe all disorders presenting With MTS posure in children. Drs. Paritosh Khanna seen on aXial images (Figure 1), and include on brain imaging, including COACH and AndreW PoliakoV then take us (Cerebellar Vermis hYpoplasia, Oligophrenia, Vermis hYpoplasia and thick, elongated and through some deVeloping applications AtaXia, Coloboma, and Hepatic fibrosis), horiZontal superior cerebellar peduncles of fMRI techniques that Will haVe partic - Orofaciodigital tYpe VI, Dekaban-Arima, (SCP). In addition, a narroW pontomesen - ular utilitY in pediatric patients. FinallY, Malta, Senior-Løken (retinal dYstrophY/ con - cephalic junction (=isthmus) With a deep Dr. MarV Nelson has again contributed genital retinal blindness and nephronophthi - interpeduncular (IP) fossa is often seen, and another RetZius AnatomY quiZ for our sis - NPH) and other Cerebello-Oculo-Renal horiZontal (but not thick) SCP haVe been de - entertainment and edification. sYndromes (CORS). scribed in a “mild” MTS, usuallY seen With JSRD are clinicallY heterogeneous condi - homoZogous NPHP1 mutations (Figure 2). RespectfullY, tions characteriZed bY core features of hYpo - Sometimes, the MTS is not obVious in a Dennis ShaW, M.D. tonia, ataXia, intellectual disabilitY and single aXial image, so it is essential to look for Seattle Children’s Hospital Variable inVolVement of the retina, kidneY, the component features in all three planes. Seattle, Washington liVer and other tissues/organs in subsets of On sagittal images, the roof of the fourth patients. The preValence of JSRD has been Ventricle is oriented more horiZontallY and estimated to be ~1/100,000 liVe births; hoW - the fastigium is positioned more superiorlY eVer, theY are almost certainlY under-diag - than usual (Figure 3). The fourth Ventricle nosed. opens WidelY immediatelY distal to the aque - Ten genes responsible for JSRD haVe duct (rather than graduallY tapering) and the A B C been described so far, accounting for ~50% foramen of Magendie is often enlarged. of patients. These genes encode proteins These findings reflect the horiZontal SCP and that localiZe to the primarY cilium and/or cerebellar Vermian hYpoplasia. The Vermis basal bodY making JSRD part of an eXpand - Varies from mildlY hYpoplastic to absent and ing group of conditions called “ciliopathies.” is more seVere posteriorlY than anteriorlY, PrimarY cilia mediate mechano-, chemo- and often With dYsplasia of the anterior Vermis. light sensation, as Well as major signal trans - Midline clefting is frequentlY seen rostrallY on duction pathWaYs, and cilia are inVolVed in coronal images (Figure 4). Diffusion tensor imaging (DTI) demon - deVelopment and function oEf manY tissues F and organs including the brain, retina, kid - neY, liVer, skeleton and limbs, accounting for MTS continued on page 2 MTS continued from page 1 KidneY: Renal disease occurs in 25% THE RETZIUS of patients, ranging from nephronophthi - NEUROANATOMY strates lack of decussation of the SCP at sis (NPH), (most commonlY) to cYstic dYs - the pontomesencephalic junction and plasia that oVerlaps With Meckel QUIZ #8 lack of decussation of the corticospinal sYndrome. On ultrasound, NPH presents tracts at the medullarY pYramids (Figure as normal-siZed echogenic kidneYs pro - 5). In addition, DTI can shoW lateraliZa - gressing to small cYsts at the corti - Name the structure with the arrow on tion of the deep cerebellar nuclei. comedullarY junction With loss of this coronal section through the brain. Additional neuroimaging findings in - corticomedullarY differentiation. CDK clude encephalocele, agenesis of the presents as large kidneYs and multiple corpus callosum, VentriculomegalY, hY - cYsts such as seen in Dekaban-Arima sYn - drocephalus, posterior fossa cYsts, cere - drome. bellar and cerebral heterotopia, LiVer: Congenital hepatic fibrosis oc - polYmicrogYria, hYpothalamic hamar - curs in 18 % presenting as a spectrum of toma and absence of the pituitarY gland. disease from persistentlY eleVated DYsplasia of the deep cerebellar nuclei, transaminases, to hepatosplenomegalY, inferior oliVarY nuclei and multiple cranial to portal hYpertension requiring por - nerVe nuclei, and heterotopias of tosYstemic shunting or resulting in upper Purkinje-like neurons haVe been noted in gastrointestinal bleeding. autopsY specimens. Skeletal: PolYdactYlY is seen in 16%. The pathologY underlYing the MTS Most commonlY it is postaXial, folloWed appears to be an aXon guidance defect, bY preaXial and rarelY mesaXial, VariablY as eVidenced bY the lack of decussation affecting the hands and feet. RecentlY, of the SCP. The absence of the crossing patients With both JSRD and Jeune as - ANSWER TO RETZIUS NEUROANATOMY fibers at the pontomesencenphalic junc - phYXiating thoracic dYstrophY haVe been described based on clinical presentation QUIZ ON PAGE 5 tion likelY also results in the decreased AP dimension of the isthmus and deep and plain films demonstrating shortened interpeduncular cistern. long bones and trident acetabulae, indi - cating that some genes maY cause both Neurological features: of these conditions. Scoliosis due to hY - If not detected prenatallY, patients potonia is also a reasonablY frequent With JSRD tYpicallY present With signs of complication. cerebellum and brainstem dYsfunction. Infantile hYpotonia eVolVes into motor Diagnosis and Management: delaYs and ataXia later in life. EXpressiVe After the diagnosis of MTS on brain communication (speech) is often more MRI, a search for multi-organ inVolVement seVerelY affected than receptiVe commu - should be undertaken to alloW earlY treat - nication due to the motor impairment. ment of medical complications. CognitiVe outcomes range from seVere ProgressiVe renal, liVer and retinal findings intellectual disabilitY to tYpical range in - maY remain asYmptomatic for manY Years. IN THIS ISSUE: telligence. EYe moVement abnormalities Guidelines for management of patients Introduction 1 are inVariant and include oculomotor With JSRD haVe been deVeloped including Clinical Insights: The Molar Tooth Sign (MTS): apraXia and nYstagmus. Strabismus and YearlY ophthalmologic eValuation, Joubert SYndrome and Related Disorders 1 ptosis are also common. Alternating renal/liVer US, urinalYsis, serum transamni - tachYpnea/apnea is a distinctiVe feature nases, BUN and creatinine measurement. The RetZius NeuroanatomY QuiZ 2 seen in manY infants, reflecting disor - LiVer MRI maY be useful for diagnosis MinimiZing Radiation EXposure in dered central respiratorY control in the When liVer fibrosis is suspected. Childhood HYdrosephalus: brainstem. Classification of JSRD is still eVolVing but it LoW dose CT and limited MRI 4 is hoped that the emerging phenotYpe- Sedated Functional MRI (fMRI) and Functional Eye and extra central nervous genotYpe correlation maY simplifY the connectiVitY MRI (fcMRI) in Pediatric system involvement: quest for a causatiVe gene in an affected Neuroimaging 6 EYe: Retinal dYstrophY With Visual loss indiVidual in a purpose to prioritiZe testing Web Sites of Interest 5 is present in a ~25% of patients With and saVing moneY and time. Meetings of Interest 8 JSRD and ranges from congenital blind - ness (Leber Congenital Amaurosis) to Genetic counseling and Message from the President 9 adult-onset nYctalopia (night blindness). prenatal diagnosis: In addition, chorioretinal colobomata are JSRD is predominantlY autosomal EDITOR seen, particularlY in patients With DENNIS SHAW, MD COACH sYndrome. MTS continued on page 3 2 ASPNR
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