síndrome de moebius
Transcripción
síndrome de moebius
HOSPITAL CLÍNICO SAN BORJA ARRIARÁN SERVICIO DE NEUROPSIQUIATRÍA INFANTIL SÍNDROME DE MOEBIUS Dr. Guillermo Fariña Kutz Neurólogo Infan.l Dra. Daniela CasHllo Villagrán Residente Neurología Infan.l Mayo 2014 SÍNDROME DE MOEBIUS DEFINICIÓN DEBILIDAD FACIAL CONGÉNITA ASOCIADA A ALTERACIÓN EN LA ABDUCCIÓN OCULAR Developmental facial paralysis • Se debe, en parte, a la pérdida de la función de nervios craneales motores • La mayoría de los casos se diagnos.can durante la infancia Developmental facial paralysis • Es una enfermedad no progresiva 1321 Figure 2 Example of classical Möbius syndrome case. Preoperative picture of a 9-year old boy palsy (Möbius syndrome), left side more involved than the right. Note the absence of expression (Figure 2a). Neurological examination in addition to the bilateral seventh nerve involvement ( (III) bilaterally, (inability to gaze upward), bilateral sixth (VI) (paralysis of lateral gaze) and undergone a left otoplasty for correction of prominent ear deformity and a static fascial slin performed elsewhere at a younger age. He was treated with a two-stage free gracilis muscl motor fibers from the contralateral facial nerve. Secondary revisional surgery took place tw temporalis pedicle transfer to the left commissure. Appearance of the patient in his last follo surgery (Figure 2b). talipes equinovarus, syndactyly, hemimelia, Poland’s anomaly, craniofacial deformities, etc. (Figures 3 and 4). Hemifacial microsomia (HFM) Figure 2 vascular disruption hypo HFM risk and other patho free radical generation,4 sure to teratogens39 an technologies have been p A common association is Hemifacial Microsomia (HFM), an Neonatal asymmetric umbrella term that covers a variety of developmental defects. HFM involves first and second branchial arch derivatives with a highly variable phenotype. Deformities The clinical hallmark o may include auricular defects, preauricular tags and appearance at rest, but s fistulae, microtia-atresia, mandibular, maxillary, and the lower lip with crying orbital hypoplasia, micropthalmia, epibulbar dermoid, been used to characteriz Example of classical Möbius syndrome case. Preoperative picture of a 9-year oldhearing boy withloss, bilateral facial strabismus, conductive or sensoneural and developmental crying faces, congenital h SÍNDROME DE MOEBIUS HISTORIA 1880 Von Graefe describe un caso de diplejía facial congénita Leipzig, W Engelman. 1880;6:60. 1888 y 1892 El síndrome es descrito con más detalle por Paul Julius Möbius, neurólogo alemán Munchen Medizinische Wochenschri7. 1888;35:91-‐4. Munchen Medizinische Wochenschri7. 1892;39:17-‐21, 41-‐3, 55-‐8. Von Graefe y Möbius aceptaron sólo casos con DIPLEJÍA FACIAL CONGÉNITA Y PARÁLISIS DEL VI P.C. BILATERAL para consHtuir el síndrome de Moebius SÍNDROME DE MOEBIUS HISTORIA 381 1939 Henderson amplía la definición e incluye casos con parálisis facial congénita UNILATERAL THE CONGENITAL FACIAL DIPLEGIA SYNDROME: CLINICAL FEATURES, PATHOLOGY AND ETIOLOGY. 1 A REVIEW OF SIXTY-ONE CASES (From the Department • University of Edinburgh.) Brain. 1939;62:381-‐403. paralysis of cranial nerves is sufficiently rare to attract special attention. The ocular and facial nerves are those most frequently and thela anatomical relationships of thedlatter render them suscep- entre En la aaffected ctualidad, definición y criterios iagnósHcos varían tible to paralysis from a greater variety of causes. Thus, there are several autores types of congenital facial palsy. The intra-partum types predominate and, with the extremely rare exception of bilateral peripheral trauma, they are Algunos más restric.vos en su definición, requieren la presencia de all unilateral. Of the ante-partum types, however, the bilateral variety is una anomalía congénita musculoesqueléHca para hnerve acer el the commonest and is usually associated with other cranial palsies. This paper is solely concerned with the ante-partum bilateral type. diagnós.co A child displaying many typical features of the condition was seen recently at the Royal Edinburgh Hospital for Sick Children. Perusal of the relevant literature showed that no adequate review of the published CONGENITAL • of Child Life and Health, Downloaded from http://brain.oxfordjournals.org/ at Univers BY J. L. HENDERSON URRENT C OPINION Congenital cranial dysinnervation disorders: a concept in evolution Thomas M. Bosley a, Khaled K. Abu-Amero a,b, and Darren T. Oystreck a,c Curr Opin Ophthalmol. 2013 Sep;24(5):398-‐406. Purpose of review We review the congenital and genetic diagnoses that are currently included in the congenital cranial dysinnervation disorders (CCDDs). • Hace más de 60 años à Ciertos niños nacen con alt. de la mo.lidad ocular aRecent sociados findings a músculos extraoculares fibró.cos Recent literature contains new genotypic and phenotypic descriptions of Duane retraction syndrome, Moebius syndrome, and other CCDDs. New genes which when mutated can result in CCDD have been identified, permitting a better understanding of associated phenotypes. More information is available regarding neurodevelopmental and clinicalceffects of various gene associated with individual Concepto de “fibrosis ongénita de lmutations os músculos CCDDs. For certain CCDDs, the phenotype of a particular individual may not completely predict the genotype, and conversely, the genotype may not always predict the phenotype. extraoculares” (CFEOM) Summary The CCDD concept has focused attention on specific congenital disturbances of human ocular motility and on the fact that these disorders are typically neurogenic in origin. The past decade has seen rapid evolution within this field with the last 2 years yielding additional information about existing diagnoses, genes, and phenotypes that may result in better classification of these disorders and new genotype– phenotype correlations in the future. • Síndrome de retracción de Duane (DRS) y el síndrome de Moebius Keywords (MBS) fbrainstem ueron development, reconocidos omo patologías únicas desde n strabismus congenitalccranial dysinnervation disorders, cranial nerves, ocularumotility, principio INTRODUCTION Ophthalmologists recognized over 60 years ago that certain children were born with congenital ocular motility abnormalities associated with restricted nerve development. It is likely that we have not yet identified all syndromes that would fall under the CCDD rubric, although presumably the ones not yet identified are less common (or at least harder to DESÓRDENES DE DESINERVACIÓN CRANEAL CONGÉNITA • La evidencia acumulada muestra que la mayor parte de estos síndromes tendrían una causa neurogénica • 2002 à concepto alternaHvo de “DESÓRDENES DE DESINERVACIÓN CRANEAL CONGÉNITA” (CCDD) que cambió el enfoque del desarrollo muscular • Los avances en la úl.ma década han apoyado el concepto de CCDD, con todos los genes iden.ficados hasta el momento afectarían el desarrollo del tronco cerebral y/o PC • Es probable que aún no se hayan iden.ficado todos los síndromes que caigan bajo el concepto de CCDD Bosley TM, Abu-‐Amero KK, Oystreck DT. Congenital cranial dysinnerva.on disorders: a concept in evolu.on. Curr Opin Ophthalmol. 2013 Sep; 24(5):398-‐406. 400 Table 1. Genetic classification of currently recognized CCDDsa www.co-ophthalmology.com Main category Gene Locus Phenotype Duane retraction syndrome !!! !!! Isolated Duane retraction syndrome SALL4 20q13.2 Inheritance Comments DRS !!! Unknown Prevalence "0.1%; acc all cases of incomita bilateral in 14–20% Duane-radial ray syndrome DRRS 607323 AD Rare Three unrelated patient 8q12–13 Duane retraction syndrome 1 DURS1 126800 AD 2q31.1 Duane retraction syndrome 2 DURS2 604356 AD Rare; 10 recognized m !!! Possible X chrm Wildervanck syndrome Wildervanck 314600 Unknown Females>>males 7p15.2 Bosley-Salih-Alorainy syndrome BSAS 601536 AR Rare Athabascan brainstem dysgenesis syndrome ABDS HOXA1 Volume 24 # Number 5 # September 20 Other horizontal MIM CHN1 !!! Congential fibrosis of the extraocular muscles Phenotype abbreviation !!! Multiple chrm locations Chromosomal DRS Chromosomal DRS !!! !!! Unilateral or bilateral D a wide spectrum of o developmental abno (excluding syndrome KIF21A 12q12 Congenital fibrosis of the extraocular muscles type 1A CFEOM1A 135700 AD 13 recognized mutation heterogeneity resultin phenotypes (CFEOM Congenital fibrosis of the extraocular muscles type 3B CFEOM 3B PHOX2A 11q13 Congenital fibrosis of the extraocular muscles type 2 CFEOM 2 602078 AR Five currently recognize TUBB3 16q24.3 Congenital fibrosis of the extraocular muscles type 3A CFEOM3A 600638 AD TUBB3 mutations result phenotypic heteroge recognized mutation either in isolation (C as part of a larger sy to as TUBB3 syndrom Congenital fibrosis of the extraocular muscles type 1B CFEOM1B TUBB3 syndrome TUBB3-CFEOM CFEOM1B or 3A assoc neurological symptom TUBB3-E410K-syndrome TUBB3-E410KCFEOM CFEOM associated with features. Arises from acid substitution TUBB2B 6p25.2 TUBB2B-E421K-Congenital fibrosis of the extraocular muscles TUBB2B-E421KCFEOM !!! AD Three affected members rare TUBB2B phenot CFEOM only occurs acid substitution !!! 13q12.11 Congenital fibrosis of the extraocular muscles type 3C CFEOM3C 609384 AD Four affected members Tukel syndrome CFEOM-U 609428 AR Six affected members in same family Moebius syndrome MBS 157900 Unknown Prevalence of 0.0002% births; rare chromoso !!! !!! Bosley TM, gaze Abu-‐Amero KK, Oystreck DT. Congenital cranial dysinnerva.on disorders: a concept in evolu.on. Curr Opin Ophthalmol. 2013 Sep; disorders 24(5):398-‐406. ROBO3 11q24.2 Horizontal gaze palsy and HGPPS 607313 AR 23 recognized mutation me 24 # Number 5 # September 2013 1040-8738 ! 2013 Wolters Kluwer Health | Lippincott 400 www.co-ophthalmology.com Volume 24 William # Numb TUBB2B 6p25.2 TUBB3-E410K-syndrome TUBB3-E410KCFEOM TUBB2B-E421K-Congenital fibrosis of the extraocular muscles TUBB2B-E421KCFEOM !!! AD Three affected memb rare TUBB2B phen CFEOM only occu acid substitution CFEOM3C 609384 AD Four affected membe 609428 MIM AR Inheritance Six affected members Comments same family a Table 1. Genetic classification of currently CCDDs !!! 13q12.11 recognized Congenital fibrosis of the extraocular muscles type 3C Phenotype CFEOM associated w features. Arises fro acid substitution Main category Gene Locus Tukel syndrome Phenotype CFEOM-U abbreviation Duane retraction Other horizontal syndrome !!! !!! Isolated Duane retraction Moebius syndrome syndrome MBS 157900 !!! Unknown Prevalence all casesofof0.0002 incom bilateral 14–2 births; rareinchromo SALL4 20q13.2 Duane-radial ray syndrome 8q12–13 Duane retraction syndrome 1 progressive scoliosis DRRS HGPPS 607323 607313 AD AR Rare 23 recognized mutat !!! CHN1 2q31.1 Duane retraction syndrome 2 DURS2 604356 AD Rare; 10 recognized !!! Possible X chrm Wildervanck syndrome Wildervanck 314600 Unknown Females>>males 7p15.2 Bosley-Salih-Alorainy syndrome BSAS 601536 AR Rare Athabascan brainstem dysgenesis Hereditary syndrome congenital facial ABDS Multiple chrm locations paresis 1 DRS Chromosomal Chromosomal DRS 12q12 17q21.3 Congenital of thefacial Hereditaryfibrosis congenital extraocular muscles type 1A gaze disorders !!! ROBO3 Other vertical gaze disorders Other facial motility disorders !!! HOXA1 !!! !!! !!! Congential fibrosis of the extraocular muscles KIF21A HOXB1 !!! 11q24.2 !!! 3q21-q22 10q21.3-q22.1 Horizontal gaze palsy and Isolated superior oblique palsy DRS DURS1 Isolated SOP HCFP1 126800 ——— Unknown AD 601471 Three unrelated pati Unknown AD !!! PHOX2A 1p34.1-p32 Xq24-q27.1 11q13 Several familial Rare !!! !!! Unilateral or bilatera a wide spectrum Rare developmental ab (excluding syndro CFEOM1A HCFP3 135700 614744 AD AR 13 recognized muta Four affected in heterogeneity res unrelated fam phenotypes (CFEO Hereditaryfibrosis congenital Congenital of theptosis 1 extraocular muscles type 3B PTOS13B CFEOM 178300 AD Congenital fibrosis of the extraocular muscles type 2 CFEOM 2 Hereditary congenital facial paresis 2 HCFP2 604185 AD paresis 3 !!! Prevalence "0.1%; Hereditary congenital ptosis 2 PTOS2 300245 602078 AR X-linked TUBB3 16q24.3 fibrosis of the CFEOM3A 600638 AD AD, autosomal dominant; AR, autosomal recessive; chrm, chromosome;Congenital HCFP, Hereditary congenital facial paresis; MIM, Online Mendelian Inheritance of Man number. extraocular muscles type 3A a CCDD, congenital cranial dysinnervation disorder. Rare Linkage in one Five currently recogn TUBB3 mutations res phenotypic hetero recognized mutat either in isolation as part of a large to as TUBB3 synd Congenital fibrosis of the extraocular muscles type 1B CFEOM1B TUBB3 syndrome TUBB3-CFEOM CFEOM1B or 3A as neurological sym TUBB3-E410K-syndrome TUBB3-E410KCFEOM CFEOM associated features. Arises fr acid substitution TUBB2B-E421KAD TUBB2B 6p25.2 TUBB2B-E421K-Congenital Bosley TM, Abu-‐Amero KK, O ystreck DT. Congenital cranial dysinnerva.on disorders: a concept in evolu.on. Curr O!!! pin Ophthalmol. 2013 Sep; CFEOM fibrosis of the extraocular 24(5):398-‐406. muscles Three affected memb rare TUBB2B phe CFEOM only occ Síndrome de retracción de Duane • Falta de abducción, con limitación de la aducción, retracción variable del globo ocular y estrechamiento de la hendidura palpebral en aducción • Esporádico, unilateral o bilateral, aislado o sindromá.co • Gen HOXA1 (creación o supervivencia de neuronas PC VI) o genes CHN1, SALL4 (crecimiento de axones al recto lateral) Fibrosis congénita de músc. extraoculares • Alteración de movimientos oculares horizontales y/o ver.cales, y ptosis • Unilateral o bilateral • Estrabismo divergente y posición anormal de la cabeza, en especial la elevación del mentón Parálisis de la mirada horizontal y escoliosis progresiva • Parálisis de la mirada horizontal completa o parcial congénita, sin compromiso mirada ver.cal, escoliosis progresiva de inicio precoz • Gen ROBO3 (involucrado en la decusación de tractos neurales en tronco encefálico). Bosley TM, Abu-‐Amero KK, Oystreck DT. Congenital cranial dysinnerva.on disorders: a concept in evolu.on. Curr Opin Ophthalmol. 2013 Sep; 24(5):398-‐406. troch both SALL ponti abno defec locati predi moto (CFE Cong Figure 5 Clinical syndromes in CCDDs and corresponding Assaf AA. Congenital innerva.on dysgenesis syndrome (CID)/ congenital dysinnerva.on (CCDDs). (2011) 25, 1251–1261. cranial nerves. Responsible genecranial names aredisorders given inEye italics. The To da and t CFEO CF SÍNDROME DE MOEBIUS EPIDEMIOLOGÍA • Aprox. 300 casos descritos en la literatura inglesa • Prevalencia en EEUU: 0,002-‐0,0002% de los nacimientos, o 1 caso por cada 50.000 RN Neurology. Aug 12 2003;61(3):327-‐33. • En una encuesta a nivel nacional holandés en 2003, la prevalencia fue al menos el 0,002% de los nacimientos (4 casos por cada 189.000 RN) para los años 1996-‐1998 • En 2007, la Fundación Síndrome de Moebius es.mó que 2.000 personas de todo el mundo .enen la condición Am J Matern Child Nurs. Sept/Oct, 2008;33(5):272-‐278. SÍNDROME DE MOEBIUS CLASIFICACIÓN • En 1979, Towfighi et al propuso un sistema de clasificación en base a diferencias patológicas observadas en estudios de pacientes con el síndrome Acta Neuropathol (Berl). Oct 1979;48(1):11-‐7. Grupo I Hipoplasia simple o atrofia de los núcleos PC Grupo II Lesiones primarias a nivel periférico de los PC Grupo III Necrosis focal, gliosos y calcificación en núcleos PC Grupo IV Miopaqa primaria sin lesiones en PC o SNC SIN CORRELACIÓN CLÍNICA SIGNIFICATIVA SÍNDROME DE MOEBIUS PATOGENIA • No se ha podido establecer el evento primario: Aplasia del nervio, a nivel de tronco cerebral, o muscular • Los PC que pueden estar involucrados à VI al XII, con preservación general del VIII • VII en todos los casos • VI 75% • XII minoría • PC III y IV en raras ocasiones SÍNDROME DE MOEBIUS PATOGENIA MÚLTIPLES TEORÍAS: • Moebius creía que la condición era de origen degeneraHva o tóxica y que involucraba a los núcleos de los nervios afectados • Algunos autores sugieren que se debe a una hipoplasia o agenesia congénita hereditaria de los núcleos PC • Displasia mesodérmica que involucra la musculatura derivada de los 1er y 2º arcos branquiales • Esta teoría sos.ene que los cambios del tronco cerebral son secundarios a la atrofia retrógrada de los PC SÍNDROME DE MOEBIUS PATOGENIA • Malformaciones de las extremidades asociadas a la disfunción de los PC sugieren una interrupción de la morfogénesis normal, con mayor probabilidad en las semanas 4-‐7 de gestación SÍNDROME DE MOEBIUS ETIOLOGÍA • Controversial à MulHfactorial • Por definición, las lesiones traumá.cas no son parte del síndrome Gené.ca Aprox. 2% Mayoría esporádicos Neurology. Aug 12 2003;61(3):327-‐33. Daño hipóxico/ isquémico Exposición prenatal a tóxicos SÍNDROME DE MOEBIUS ETIOLOGÍA: TEORÍA VASCULAR 1. Interrupción del flujo a nivel de la arteria basilar o regresión prematura de las arterias trigeminales primi.vas 2. Interrupción del flujo de la arteria subclavia que implica la interrupción del flujo de sangre embrionario Findings that shed new light on the possible pathogenesis of a disease or an adverse effect Maternal homocystinuria and Moebius syndrome? Vascular aetiology N Gupta, M Y Anthony Neonatal Unit, John Radcliffe Hospital, Oxford, UK Correspondence to N Gupta, [email protected] BMJ Case Reports 2011; doi:10.1136/bcr.09.2010.3331 Summary A case of Moebius syndrome is reported in an infant of a mother known to have pyridoxine-unresponsive homocystinuria. The authors SÍNDROME DE MOEBIUS ETIOLOGÍA: GENÉTICA • Síndrome listado en OMIM con gen locus 13q12.2-‐q13 • Uzumcu et al. no encontró microdeleciones en esta región críHca en 9 pacientes y excluyó varios genes candidatos (FGF9, GSH1 y CDX2) Eur J Med Genet. Sep-‐Oct 2009;52(5):315-‐20. 1977 Variante de SM con una translocación recíproca t(1p34; 13q13), en al menos 7 miembros de una familia afectada de más de 3 generaciones Ziter FA, et al. Arch Neurol. Jul 1977;34(7):437-‐42. 1991 Niña de 2 años con SM con una deleción de la banda q12.2 del cr 13 Cario.po de la madre normal Slee JJ, et al. J Med Genet. Jun 1991;28(6):413-‐4. • Ambos informes sugieren que un gen responsable se encuentra en la región 13q12.2-‐q13 -‐Online Mendelian Inheritance in Man. %157900 -‐ MOEBIUS SYNDROME; MBS. OMIM -‐ Online Mendelian Inheritance in Man. SÍNDROME DE MOEBIUS ETIOLOGÍA: GENÉTICA 1996 Gran árbol genealógico con SM AD consistente en gran parte de paresia facial bilateral asimétrica Después de la exclusión de la región 13q12.2-‐13, localizaron un gen en 3q21-‐22 Kremer H, et al. Hum Mol Genet. Sep 1996;5(9):1367-‐71. 1997 Niño con sd. Möbius-‐like (diplejía facial y ptosis pero con mov. extraoculares normales y sin anomalías esquelé.cas) con una translocación recíproca entre los cromosomas 1 y 2 (p22.3, q21.1) Nishikawa M, et al. Clin Genet. 1997;51(2):122-‐3. • También se han reportado casos familiares SÍNDROME DE MOEBIUS GENÉTICA? HERENCIA? • Debido a la inconsistencia en la definición de la patología, el rol de la herencia en el síndrome de Moebius sigue siendo poco claro • Se han descrito genealogías con herencia AD, AR, y ligada al X recesiva 102 C. Vauzelle et al. / Reproductive Toxicology 36 (2013) 98–103 Table 5 Published studies on misoprostol malformative risk. SÍNDROME DE MOEBIUS ETIOLOGÍA: TÓXICOS Author Location Methodology Reason for misoprostol use Number of women or infants use of other abortifacients Results U S EProspective O F M I S O study P R O STO L D U R I N G P R EG N A N86 CYmisoprostol-exposed A N D M Ö B I U S’ SYpregnancies N D R O M E I N I N FA N T SMajor birth defects among life births: vs. 86 pregnancies exposed to Mostly self-attempted 2/67 vs. 2/81 non-teratogens abortions (95%) RR = 1.21 (95% CI = 0.17–8.35) 31.4% in the exposed group used Birth defects in the misoprostol group: another abortifacient - constriction rings of the arms USE OF MISOPROSTOL DURING PREGNANCY AND MÖBIUS’ SYNDROME - hepatosplenomegaly, pulmonary IN INFANTS hypertension, persistent fetal circulation ARLOS E. PASTUSZAK , M.SC., LAVINIA SCHÜLER, 120 M.D., PH.D., Cexposed SPECK-MARTINS, M.D., Birth defects: 5/118 vs. 81/4575 misoprostol pregnancies Prospective cohort: Dal Pizzol Tda et al. [16], ANNE L. YNTHIA M. CORDELLO, M.D., KATIA-EDNI F.A. COELHO , M.D., FERNANDO VARGAS , M.D., DECIO BRUNONI , M.D.,OR PH=.D., pregnancies without exposure 2.64 (95% CI = 1.03–6.75) vs. 4575 Adjusted Study S on Brazil Brazilian IDA V.D. SCHWARZ , M.D.,Diabetes. MARIELA LARRANDABURU, M.D., HELOISA SAFATTLE, M.D., VERA F.A. MELONI M.D., in the misoprostol group: to misoprostol Birth,defects Gestational - myelomeningocele Misoprostol used to AND GIDEON KOREN, M.D. - clubfoot induce menstruation N Engl J Med. 1998 Jun 25;338(26):1881-‐5. - syndactyly - fingernailitdefect mended for use during pregnancy, because may ABSTRACT - microcephaly stimulate uterine contractions and cause vaginal Background Patients with upper gastrointestinal No information on other abortifacients No information on time of exposure Schüler et al. [15], Brazil ulceration may be treated with misoprostol, but it is bleeding, which may endanger fetal survival. The Major birth defects study women because it 94 combination misoprostol-exposed Prospective [17], Barbero et al. of pregnancies misoprostol and mifepristone or among life births: not recommended for pregnant self-attempted and cause vagi- vs. methotrexate 401 pregnancies exposed to vs. 8/372 Mostly contractions 5/77 Argentina may stimulate uterine has been used for the elective induc(81%) Recent data from Bra- non-teratogens = 3.80 (95% nal bleeding and abortions miscarriage. electiveRRabortion of abortion.1,2 In Brazil, whereAdjusted CI = 1.05–14.61) zil, where misoprostol is used orally and vaginally as tions are prohibited, 57 to 75 percent of women Birth defects in the misoprostol group: an abortifacient, have suggested a relation between who attempt abortion use misoprostol, which can transverse limb - encephalocele, the use of misoprostol by women in an unsuccessful misoprosbe obtained over the counter.3-5 However, constriction ring defects, attempt to terminate pregnancy and Möbius’ syntol often fails to induce abortion during the first triporencephaly drome (congenital facial paralysis) in their infants. pulmonary adenomatous cystic in mester,6 and up to 80 percent of the -pregnancies Methods We compared the frequency of misomalformation women who use this agent continue to term. prostol use during the first trimester by mothers of encephalocele - occipitalactions Although misoprostol has no teratogenic infants in whom Möbius’ syndrome was diagnosed - intestinal malrotation 7-9 10 in pregnant rats and mice, there are reports of and mothers of infants with neural-tube defects in 35.2% in the exposed group used Brazil. All diagnoses in infants were made between another Möbius’ syndrome (congenital facial paralysis, with abortifacient • Estudio de niños en Brasil de 1998 à Fuerte asociación entre SM y uso prenatal de misoprostol • Se cree que causa un evento isquémico en el tronco cerebral embrionario temprano en la gestación January 16, 1990, and May 31, 1996, by clinical genetCase-control study seven hospitals who also interviewed the self-attemptedabout abortions Mostlyinformation and recorded the admin(98%) istration of misoprostol, among other data. Results We identified 96 infants with Möbius’ Case-control study nested a Brasil et al. [14], syndrome and matched them with 96ininfants with of mean very low birth Brazil cohort neural-tube defects. The age atweight the time of the infants. syndrome was 16 months diagnosis of Möbius’ abortions of neural-tube (range, 0.5 to 78),Self-attempted and the diagnosis [10], Case-control study Orioli and Castilla defects was made within 1 week of birth in most al. [11],at Pastuszak eticists Brazil mothers or without limb defects) in infants whose mothers Misoprostol exposure among attempt at aborMoebius’syndrome vs. neural tube In one study, in a small cohort of 20 women tion. defects: who used misoprostol unsuccessfully OR as =an abortifa29.7 (95% CI = 11.6–76.0) cient during the first trimester, 3 had a second-triMisoprostol exposure among birth 37 infants with birth defects vs. 387 mester abortion, and 17 gave birth to infants without without birth defects controls: controls defects vs. study was to malformations.15 The purpose of our6/37 vs. 28/387 = 2.4 (95% CIthe = 1.0–6.2) compare the frequency of misoprostolOR use during 4673 infants with birth vs. exposure first trimester of defects pregnancy between Misoprostol mothers of in- among birth 96 took infantsmisoprostol with Moebius’syndrome vs. in an unsuccessful with neural-tube defects 96 infants 11-14 First case of Moebius-Poland syndrome in child prenatally exposed to misoprostol Sr. Editor: SÍNDROME DE MOEBIUS - El síndrome de Moebius (OMIM 157900) se caracteriza por descargado de http://zl.elsevier.es el 14/05/2014. Copia para facial uso personal, se prohíbe la transmisión de El este documento por cualquier medio o formato. con alteración de la abducción ocular. nerRev. Med. FCM-UCSG, Año 2011, vol.17 Nº1. Pparálisis áGS. 65-69 vio facial (VII nervio craneal) y nervio abducens (VI nervio ISSN - 1390-0218 craneal) son más frecuentemente involucrados, pero otros nervios craneales pueden estar involucrados también. El fenotipo es variable y puede incluir defectos congénitos oro502 CARTA faciales y de las extremidades1 . La secuencia de Poland (OMIM 173800) se caracteriza por la presencia de braquisindactilia unilateral y aplasia ipso∗ b lateral dea lay porción esternocostal del músculo pectoral Autor correspondencia. G. Salazar a,∗ , D. Cuello a , M. Fragoso L. Benlloc mayor. Algunas veces se denomina síndrome de Poland por Correo electrónico: [email protected] (G. Sal ser inicialmente descrito por Poland2 . a Servei de Neurologia, Hospital Consorci Sanitari de La combinación del síndrome de Moebius y Poland Terrassa, Barcelona, España se presenta raramente y se ha estimado una prevalendoi:10.1016/j.nrl.2011.01.020 cia de 1 en 500.000; en la literatura revisada no se b Serveicase dereport: Psiquiatría, Consorci Sanitari de Clinical Moebius Hospital syndrome associated with the use of misoprostol in pregnancy encontró esta asociación en expuestos prenatalmente a 3 Terrassa, Barcelona, España misoprostol . Figura comisura labial desviada hacia el lado Figura 1 1. Nótese fenotipo típico de síndrome de MoebiusSe presenta un reporte de síndrome de Moebius y Poland Poland, hipoplasia del pectoral con atelia y pie equinovaro. en un neonato expuesto prenatalmente a misoprostol. 1 Paciente de madre de 18 años, quien consultó por2 Callehijo Morillo , Javier Aquiles Hidalgo Acosta María Fernanda Calderón León1, Lennys Viviana dismorfismo facial, encontrándose al examen físico parálisis facial bilateral, cara redondeada, fisuras palpebrales delga1 Universidad Católica de Santiago de Guayaquil, Facultad de Ciencias Médicas, Guayaquil, Ecuador das, labios en arco de cupido, paladar ojival, micrognatia, 2 Hospital IESS, Portoviejo, Ecuador hipoplasia de pectoral mayor con ausencia de tetilla (ateel desarrollo de los vasos sanguíneos cambiando lia), además se encuentra sindactilia proximal del segundo y tercer dedo, y pie equinovaro bilateral (figs. 1 y 2). Comola estructura6,7 . Las anormalidades vascu y/o antecedente de importancia se encuentra que la madre utisubclavia derecha observada en síndrom lizo por vía oral y vaginal a las 5 semanas de gestaciónarteria 400 !g de misoprostol con fines abortivos, presentando sangrado pueden relacionarse con una disrupción vascular RESUMEN escaso. durante un período crítico5,8 . El misoprostol es un análogo sintético de la misoprostol prostaEl síndrome de Moebius conocido también como diplejia facial congénita o agenesia nuclear, una enfermedad neurológica glandina E1 aprobado según las es entidades reguladoras de congénita poco frecuente en la que se ven afectados los núcleos de origen de de los pares craneales y VII, impidiendo su total desarrollo. medicamentos muchos paísesVIpara la prevención y el tratamiento de úlceras gástricas asociadas con el uso de describe el caso clínico de un paciente de 11 meses de edad cuya madreno usó tabletas de misoprostol porantisecretor vía vaginal (400 mcg), antiinflamatorios esteroideos, por su efecto de ácidos gástricos. La exposición prenatal a misoprostol doi:10.1016/j.nrl.2011.01.019 se ha asociado a la ocurrencia de defectos por disrupción Figura 2. se observa lagoftalmia en ojo derecho vascular, principalmente la secuencia de Moebius y defectos no siendo así en el primer trimestre de gestación, donde los efectos son devastadores provocando un aborto, o en su defecto, de las extremidades de tipo terminal y transversal4,5 . Las anormalidades en la estructura vascular ser El síndrome Moebius (OMIM se caracteriza por pueden legal, el misoprostol sede emplea para la interrupción del 157900) embarazo, sin embargo la infrecuente supervisión profesional, llevan a Figura 2 Nótese la parálisis facial bilateral, característica secundarias a efectos teratógenos. Los teratógenos pueden típica del síndrome de Moebius. parálisis facial con alteración de la abducción ocular. El actuar directamente disminuyendo el nerflujo sanguíneo o en de anomalías congénitas. El presente trabajo demuestra la injerencia del misoprostol como agente teratógeno durante el primer trimestre de embarazo inductor al desarrolloydel síndrome abducens de Moebius. vio facial (VIIy posible nervio craneal) nervio (VI nervio Palabras clave Reporte de caso clínico: síndrome de Moebius asociado al uso de misoprostol en el embarazo Primer caso de síndrome de Moebius-Poland en niño expuesto prenatalmente a misoprostol First case of Moebius-Poland syndrome in child prenatally exposed to misoprostol Sr. Editor: SÍNDROME DE MOEBIUS ETIOLOGÍA: TÓXICOS • Otros tóxicos descritos asociados: • Ergotamina • Cocaína • Fármaco: Zonisamida -‐Smets K, at al. Ergotamine as a possible cause of Möbius sequence: addi.onal clinical observa.on. J Child Neurol. May 2004;19(5):398. -‐Puvabanditsin S, et al. Poland-‐Möbius syndrome and cocaine abuse: a relook at vascular e.ology. Pediatr Neurol. Apr 2005;32(4):285-‐7. -‐Kanemoto N, et al. A case of Moebius syndrome presen.ng with congenital bilateral vocal cord paralysis. Eur J Pediatr. Aug 2007;166(8):831-‐3. SÍNDROME DE MOEBIUS CUADRO CLÍNICO Figura 1. Paresia de la musculatura frontal izquierda Parálisis Facial Espectro au.sta Discapacidad Intelectual Hipogonadismo? Figuras 2. Sonrisa asimétrica, por la paresia facial SÍNDROME DE MOEBIUS PARÁLISIS FACIAL • La diplejía facial es el síntoma más notable • Puede ser observado poco después del nacimiento • Cierre incompleto del párpado durante el sueño • Babeo y dificultad para la succión • Incapacidad para cerrar los labios, prominencia del labio superior • En adultos à Labio inferior generalmente ever.do y prominente TRASTORNOS DEL HABLA à 76-‐90% • • • • Comp. funcional de labios, lengua, paladar, laringe Malformaciones orofaciales: paladar hendido, microgna.a y microglosia DI o pérdida de la audición Disartria flácida Briegel W. Neuropsychiatric findings of Mobius sequence -‐-‐ a review. Clin Genet. Aug 2006;70(2):91-‐7. SÍNDROME DE MOEBIUS ESPECTRO AUTISTA • En 1989, Gillberg y Steffenburg à Síntomas auHstas presentes en el 30-‐40% de niños y adultos jóvenes con SM Acta Paediatr Scand. Mar 1989;78(2):314-‐6 • Confirmado en otras series: Neuropsychiatry of Möbius sequence Table 1. The occurrence of autistic disorders in recent studies on Möbius sequence Studies Gillberg and Steffenburg (47) Johansson et al. (48) Bandim et al. (12) Verzijl et al. (2) Autistic patients 5/17 6/22 5/23 2/37 Mental retardation among autistic patients (%) 80 100 100 No information Patients’ age (years) Autism-specific instruments Classification systems 2–34 Check-list for autism (11) DSM-III-R 1–22 1–11 0.5–53 ABC, CARS, ADI-R CARS No information DSM-III-R, ICD-10 DSM-IV No information ABC, Autism Behaviour Check-List (66); ADI-R, Autism Diagnostic Interview Revised (68); CARS, Childhood Autism-Rating Scale (67). be extensively reduced or even impossible due to and in-time treatment of deficits. For many pacranial nerve palsies. Other diagnostic difficulties tients, contact to and support by the Möbius result from developmental delays, especially foundation could be very helpful. and language delays, and – most all –Clin Genet. Aug 2006;70(2):91-‐7. Briegel speech W. Neuropsychiatric findings of Mobius sequence -‐-‐ a of review. Möbius SÍNDROME DE MOEBIUS • Johansson et al. à 45% Research in Developmental Disabili.es 31 (2010) 9–24 • Briegel et al. à Sin asociación en pacientes sin DI Research in Developmental Disabili.es 31 (2010) 1462–1466 Total group Diagnosed re ASC Total group Age range, yrs Mean age (S.D.), yrs CI, yrs Diagnosed Age range, yrs Mean age (S.D.), yrs CI, yrs ASCd,e AD ALC AT AT? No suspicion of ASCs DB Too young Cognitive levelh A NA MMR SMR PMR Too young Visual impairmenti VI n = 25 (Male:female) n = 25 n = 21a (18:7) (16:5) 1 month–55 12:4 (11:7) 7:6-17:1 1:11–55 13:11 (11:5) 8:10–19:0 10 6 (MMR 2, SMR 4) 1 (MMR) 3 (NA 3) 3 (A 2, NA 1) 8 (A 6, NA 2) 4 (A 1, SMR 1)f 9 6 3 5 2 No subjects with PSVI/SVI. Data on number of subjects with VI not available. PSVI SVI Hearing impairmentj Bilateral 5/19 Data on severity of hearing impairment not available. SÍNDROME DE MOEBIUS DISCAPACIDAD INTELECTUAL • La inteligencia suele ser normal • DI LEVE à Aprox. el 10-‐15% de los pacientes • Muchos autores señalan que sin pruebas formales, la inteligencia puede estar subes.mada debido a la apariencia facial del paciente • Verzijl et al no encontró ninguna disminución en el CI, capacidad de concentración o de memoria en 12 adultos con SM, en comparación con la población sana J Neurol. 2005 Feb;252(2):202-‐7. Briegel W. Neuropsychiatric findings of Mobius sequence -‐-‐ a review. Clin Genet. Aug 2006;70(2):91-‐7. for Möbius patients. conclusion was also Compared with the children German normative sample, ourtostudy dailymore livingappropriate skills domain: standard score –This below 20, age equivaeducation or university. Seven or adolescents went thesocialization finding that GIT scoresstandard were more in accorpopulation hadto significantly resultswho for Full Scale and lent –supported 2 years, by 1 m; domain: score – 40, ‘Gymnasium’ , and two ‘Realschule’. lower All subjects attended dance with education levels than the WAIS-III scores. Performance IQ, Perceptual Organization Index and Processing ‘Gymnasium’ made good grades, and none of them received age equivalent – 2 years, 0 m; adaptive behaviour composite: Taking account these– results Speed Index. In contrast, their Verbal Comprehension standard scoreinto – 26, percentile <<0.1. by Verzijl and colleagues special assistance at school. Additionally, two subjects attendedIndex was significantly higher. Results for all performance subtests (2005) and our own study findings, we argue that the WISC-III All other probands were assessed with the WISC-III. Results a school specialized in providing education for students with were significantly worse whereas verbal subtests were, at least, is not an adequate predictor for academic success in Möbius special needs with one of them attending a school for mentally are shown in Table 1. Only one boy had a Full Scale IQ below 70, patients, and that intelligence tests should be employed that are not significantly different. thus meetingand ICD-10 retarded students. W. Briegel, M. Schimek, D. Knapp, R. Holderbach, P. Wenzel E.-M.criteria Knappfor mental retardation. As we did not include a matched control group in our study, less dependant on time constraints. No significant differences for any of the WISC-III subtests or Four subjects hadargue already been seen by a child and and adolescent Department ofthat Child and Adolescent Psychotherapy, one might our data reflect Psychiatry a bias from the composi-Leopoldina Hospital, Schweinfurt, Germany scales could be found between males and females, subjects with psychiatrist. children had being attention deficit/hyperactivity Accepted for publication 7 December 2008to the German norm tion Two of our group not matched Journal c ompila.on © 2 009 B lackwell P ublishing L td, C hild: care, himpairment ealth and development, 35, 5, 650–655 or without of ocular adduction, and children with disorder and were with methylphenidate, subject that group of medicated the WISC-III; however, we have oneone indication Key messages or without congenital malformations of the upper extremities. suffered from social phobia medication), one subject this explanation is less(no likely: The standardand deviations of the Full had no ICD-10 Another child was treated with lamScale IQdiagnosis. (SD = 14.837), theAbstract Verbal IQ (15.313) and the Perfor- Significant differences could be found between Verbal IQ and • Standardized intelligence testing with the WISC-III reveals Background Möbius sequence is a rare condition usually as unior bilateral congenital Performance IQ (Pdefined = 0.002), Verbal Comprehension Index and otrigine because of(15.835) seizures.are almost identical to that of the German mance IQ mentalMental retardation in 9%isofestimated childrentoand adolescents with facial weakness with impairment of ocular abduction. retardation occur in norm group (SD = 15.0). Perceptual Organization Index (P = 0.005), and Freedom from Möbius sequence. 10–15% of cases, but at present there have been no studies focusing on the intellectual capacities Another remarkable result of this study is that Full Scale IQ of Distractibility Index and Processing Speed Index (P = 0.024). • Compared with the general population, subjects with of children and adolescents with Möbius sequence. Intellectual performance Möbius patients does not seem to predict academic success of According to thesequence WISC-III manual (Tewes etlower al. 2000), 18/21 Möbius Methods Twenty-three children and adolescents aged 6–16 years achieve could be significantly recruited following a results for Möbius patients. All probands who attended ‘Gymnasium’ subjects had a significantly higher (P < 0.05) Verbal than PerIntelligence assessment took aboutrequest 2 h and was performed of the German Möbius in foundation. TheFull primary of all subjects out a special Scalecaregivers IQ, Performance IQ,filled Perceptual Organization made good grades, even though their average Full Scale IQ was formance IQ, and andProcessing 20/21 showed significantly higher scores for the morning. questionnaire to compile personal, somatic andIndex psychosocial history ofSpeed the probands. All significantly subjects Index, but higher about 92, and their mean Performance IQ was below average. In examination. assessthe intellectual capacities, the German version the Wechsler Verbal Comprehension Index thanoffor the Perceptual OrgaOne boy, aged 11 years, could had nota physical be examined withTothe results for Verbal Comprehension Index. • contrast, En caso de students DI severa à E scala d e usually pursuing the highest educational Intelligence Test-III (WISC-III) was administered. In case of aIQ severe mental retardation, the seem Vineland nization Index. WISC-III as he was both mentally and physically severely handi• Full Scale of the WISC-III does not to be a good Cognitive evaluation in children and adolescents with Möbius sequence • 23 pacientes, 6-‐16 años • Se aplicó la versión alemana del WISC-‐III route, ‘Gymnasium’, are expected toBehavior have at Rating least high Vineland Adaptive Formaverage was used as anpredictor alternative. for academic success in Möbius patients. Keywords Full Scale IQ. Table 1. IQ scales, indices and subtests of the Wechsler Intelligence Test-III: minimum and maximum values, means,years] standard deviations and children and adolescents, Results Twenty-two subjects [12 males, 10 females; mean age: 11.3 (6–16) could be intelligence, mental comparison with the normative sample There are several hypothetical explanations the discrepincluded; 21 could be for examined with the WISC-III. Compared with the normative sample, Full Scale retardation, Möbius ancy between going to ‘Gymnasium’ with a low average IQ (mean: 92.05; standard deviation:Full 14.84) was significantly lower (P = 0.023) which was the Comparison with sequence IQ scale/index Minimum Maximum Mean 80.48; standard Standard deviation normative sample Scale IQ and doing well there. For one,ofparents may strongly IQ (mean: consequence a very low Performance deviation: 15.84). Compared with Acknowledgements Correspondence: the76 normative sample, the results of all performance were significantly lower the prestigious ‘Gymnasium’ Verbal IQ advocate for their child to attend 144 106.24 subtests 15.313 n.s. Dr Wolfgang Briegel, (P = 0.033–0.000), whereas verbal subtest scores did not differ or were eventohigher [‘Similarities’ which might be as well an explanation as a school placement Performance IQ Klinik für Kinder- und 56 127 15.835 LowerDeutschland (P = 0.000) The80.48 authors are very grateful Moebius Syndrom Full Scale IQwith some 65 92.05 14.837 Lower (P = 0.023) of Jugendpsychiatrie und While (P = 0.026) and have ‘Vocabulary’ (P = 0.019)]. Verbal IQ (mean: 106.24; standard deviation: 15.31) was not assistance. we do not any135 information e.V., the German Möbius foundation, and to all participants Psychotherapie, Verbal Comprehension Index 77 143the normative sample. 108.33 15.078 Higher (P = 0.020) significantly different from Two boys met ICD-10 criteria for mental aboutLeopoldina the firstKrankenhaus, aspect, to our knowledge, none of the children this study. They also want to thank Prof Regina Bussing, GainesPerceptual Organization Index 53 15.609 Lower (P = 0.000) Full Scale IQ124 was not predictive for81.14 academic success. Gustav-Adolf-Straße 4, received special Index assistance atretardation. the ‘Gymnasium’ . Another possible ville, Florida, for help with the manuscript. n.s. Freedom from Distractibility 57 130 99.19 16.857 97422 Schweinfurt, Conclusions The WISC-III is notisanthat adequate predictor for academic success in Möbius patients; mentioned above Processing explanation SpeedGermany Index for the discrepancies 60 103 83.14 11.829 Lower (P = 0.000) intelligence tests which are less dependant on time constraints should be preferred for subjects E-mail: is not really appropriate for subjects with Möbius the WISC Comparison with [email protected] with Möbius sequence. References sequence. Verbal subtests Minimum Maximum Mean Standard deviation normative sample Up to date, only one study with a primary focus on cognitive Amaya, J. & Taylor, D. (1990) Möbius Information 3 16 10.57L. G., Walker,2.731 n.s.syndrome: a reported, an Similarities capacities of adults with Möbius7sequence has been18 11.48and report of2.804 Higher (P5,= 0.026) study 18 cases. Binocular Vision Quarterly, SÍNDROME DE MOEBIUS EXAMEN FÍSICO • Los hallazgos {sicos dependen de la definición de caso del SM • Al u.lizar la definición más comúnmente aceptada, la apariencia qpica fenoqpica es un aspecto de cara hipomímica con diversas parálisis de la mirada FACIE DE MÁSCARA Dificultades para relacionarse con otras personas • • • • Parálisis de oculares externos, incluyendo ptosis à 80% de los pacientes ConjunHviHs recurrente o crónica Opacidades corneales inusuales Disfagia común SÍNDROME DE MOEBIUS EXAMEN FÍSICO Anomalías menos frecuentes: • Dextrocardia, artrogriposis múlHple congénita • Alt. de la piel: Pigmentación café-‐au-‐lait, ausencia de tejido subcutáneo • Un caso con parálisis cordal bilateral congénita fue reportado por Kanemoto en 2007 Eur J Pediatr. Aug 2007;166(8):831-‐3. SÍNDROME DE MOEBIUS PARÁLISIS DEL NERVIO ABDUCENS • Parálisis del VI PC se presenta en aprox. el 75% de los pacientes • La mayoría bilateral y generalmente completa • Es la única parálisis ocular en aprox. el 50% de los pacientes • Los niños afectados pueden nacer con un estrabismo convergente marcado SÍNDROME DE MOEBIUS Carta et al ! Möbius Syndrome: An Italian Case Series Figure 1. A, Möbius syndrome pattern A: eyes are fixed in straight position with a complete Ophthalmology deficit of both abduction adduction; Volume 1and 18, N umber 8, objects August moving 2011 laterally are followed by large head movements. AI, Bilateral injury of the entire VIth and VIIth cranial nerves, other than superior lacrimal nuclei (outlined area), may be responsible for a balanced but opposite muscles palsy. B, Möbius syndrome pattern B: large angle esotropia with crossed fixation and incomplete deficit of both abduction and adduction. BI, Bilateral lesion of the ventral portion of the VIth cranial nerve nucleus sparing its dorsal portion (outlined area) can allow overaction of the medial rectus, thus producing esotropia. C, Möbius syndrome pattern C: large-angle exotropia with vertical misalignment. CI, Bilateral injury affecting the lower brainstem with another one located in proximity of the mesencephalic center for vertical SÍNDROME DE MOEBIUS COMPROMISO DEL NERVIO HIPOGLOSO • Es el 3er PC más frecuentemente afectado y está implicado en aprox. el 25% de los casos reportados • Atrofia de la lengua • Incapacidad para protuirla • Fasciculaciones • Los músculos oculares están siempre involucrados cuando la lengua se ve afectada ORIGINAL Manifestaciones oculares y sistémicas del síndrome de Möebius! A.M. Borbolla Pertierra ∗ , P. Acevedo González, V. Bosch Canto, J.C. Ordaz Favila y J.C. Juárez Echenique Servicio de Oftalmología Pediátrica, Instituto Nacional de Pediatría, México Distrito Federal, México ediatr (Barc). 014. h}p://dx.doi.org/10.1016/j.anpedi.2013.10.023 10 Pde octubre de 22013 Recibido el 23 de junio de 2013; aceptado elAn • • Documento descargado de http://zl.elsevier.es el 11/05/2014. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. 64 expedientes clínicos +Model Resumen PALABRAS CLAVE Limitación a la abducción (100%), parálisis facial (100%), endotropia (54%), ANPEDI-1436; No. of Pages 6 IN PRESS Introducción: El síndrome de Möebius ARTICLE es una enfermedad caracterizada por en los núcleos Síndrome de Möebius; epicanto ( 51,5%), e ntropión ( 22%) y a ntec. d e u so d e a bor.vos e n la lesión madre del sexto y séptimo nervios craneales, produciendo parálisis facial y limitación a la abducción Endotropia; A.M principalmente. El objetivo es (describir los hallazgos oftalmológicos del síndrome de Möebius Parálisis facial; durante el primer 4 trimestre d e e mbarazo 28%). en niños mexicanos. Agentes abortivos; Epicanto; Entropión Pacientes y métodos: Estudio retrospectivo, transversal, observacional y descriptivo. Se revi- En nuestro estudio predominó el Tabla 2saron Hallazgos en los párpados y los anexos expedientes clínicos de los pacientes con síndrome de Möebius del Instituto Nacional de sin embargo en otras series se ha e ción muy similar entre sexos39,40 . Resultados: Se revisaron 64 expedientes clínicos. Los hallazgos más importantes fueron limitaLa etiología de este síndrome aú Epicanto 33 endotropia (54%), epicanto ción a la abducción (100%), parálisis facial (100%) (51,5%), entropión propuesto una causa genética y una (22%) y antecedente de uso de abortivos en la trimestre de embarazo Lagoftalmos 21madre durante el primer seexotropia ha descrito la aparición del síndr (28%). Sin embargo, también se presentaron 14 hallazgos atípicos como e hipertropia. Entropión Conclusiones: El síndrome de Möebius tiene una amplia gama de manifestaciones oftalmológicas uso del misoprostol durante el em Telecanto 12 que se deben detectar temprano para mejorar su función y estética. luar nuestros resultados observam Epibléfaron 11 © 2013 Asociación Española de Pediatría. Publicado por Elsevier España, S.L. los derechos parte deTodos las madres de nuestros pa Hendiduras antimongoloides 10 reservados. como antecedente el uso de algún Ptosis 7 las primeras etapas de la gestación Hendiduras mongoloides 4 gatorio dirigido a establecer su uso Eye and systemic manifestations of Mobius Euribléfaron 1 syndrome (17,1%) que reconocieron la ingest Estenosis vía lagrimal 1 Abstract casos (9,3%) la utilización de té co Hemangioma 1 by damage in the Introduction: Mobius syndrome is characterized nucleus of the sixth and nicas. Tomando en cuenta que es seventh cranial nerves, with subsequent facial palsy and abduction limitation of the eyes. The ser más elevados si se realizara u Pediatría de México atendidos entre los añosN. 2000 y 2010. o Hallazgo pacientes KEYWORDS Mobius Syndrome; Facial palsy; Esotropia; Abortion inducing B) Right brachysyndactyly. SÍNDROME DE MOEBIUS Table 3. Horizontal ocular alignment in primary gaze position of patients with Möbius sequence from Brazil and Italy ALTERACIONES MÚSCULO-‐ESQUELÉTICAS Groups Ocular Motility Brazilian (n=46) Italian (n=20) P value* Orthotropia 13 (28.3%) 8 (40.0%) 0.3959 Esotropia 18 (39.1%) 8 (40.0%) 1.0000 08 (17.4%) 3 (15.0%) 1.0000 • Se producen en un 1/3 o más de lExotropia os pacientes *= Fisher’s exact test • • • • • • Pie bot Braquidac.lia, sindac.lia Amputaciones congénitas Artrogriposis Extremidades más pequeñas Anomalía de Poland J. C. Rucker et al. Table 4. Systemic anomalies in Möbius sequence patients from Brazil and Italy Groups Anomalies Brazilian (n=46) Italian (n=20) P value* Limb 27 (58.7%) 12 (60.0%) 1.0000 Club foot 26 (56.5%) 10 (50.0%) 0.7886 Incomplete closure of the eyelid 23 (50.0%) 15 (75.0%) 0.1027 Tongue 20 (43.5%) 11 (55.0%) 0.4310 *= Fisher’s exact test A B Figure 2. Brazilian patient with Möbius sequence presenting upper and lower limb defects. A) Amputation defect in left upper limb. B) Bilateral feet deformity with amputation defects on the left foot. 204 Arq Bras Oftalmol. 2012;75(3):202-6 arteries, and/o potentially be teratogenic ag factors, low p fectious and c with easy acce of birth defec Misoprost for legal and i and Central A ses in which m unstable fami sent study, the stable relation majority of th with a signific Various ca defects and a with the use o of Möbius seq gestational we of misoprosto the current st The reality is a delicate religious, and dividuals with of more than An increased the Italian po tically signific group. Memo bias might be to the fact tha when the mo of contracept contributing t Some ca of significant series, there is first trimester terminal trans SÍNDROME DE MOEBIUS ANOMALÍA DE POLAND Documento descargado de http://zl.elsevier.es el 14/05/2014. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. 502 G. Salazar a,∗ , D. Cuello a , M. Fragoso a y L. Benlloc b CARTA AL EDITOR Autor correspondencia. Correo electrónico: [email protected] (G. Salazar) ∗ de Neurologia, Consorci Sanitari de SM .ene aplasia o • Se es.ma que eTerrassa, l Servei 15% de los Hospital pacientes con Barcelona, España Servei de Psiquiatría, Hospital Consorci Sanitari de hipoplasia de grupos musculares a nivel del tronco Terrassa, Barcelona, España a b doi:10.1016/j.nrl.2011.01.020 • Músculos pectorales, trapecio, laqsimo del dorso, músculos abdominales externos, serrato anterior, y músculos intercostales Primer caso de síndrome de Moebius-Poland en niño expuesto prenatalmente a misoprostol el desarrollo de los vasos sanguíneos cambiando la anatomía y/o la estructura6,7 . Las anormalidades vasculares de la arteria subclavia derecha observada en síndrome de Poland pueden relacionarse con una disrupción vascular causada por misoprostol durante un período crítico5,8 . • Primera vez asociada con el síndrome de Moebius en 1973 • Generalmente uFirst nilateral y está asociada on hipoplasia mamaria case of Moebius-Poland syndrome incchild prenatally exposed to misoprostol Sr. Editor: A neonate with poland-mobius syndrome El síndrome de Moebius (OMIM 157900) se caracteriza por parálisis facial con alteración de la abducción ocular. El nervio facial (VII nervio craneal) y nervio abducens (VI nervio craneal) son más frecuentemente involucrados, pero otros nervios craneales pueden estar involucrados también. El fenotipo es variable y puede incluir defectos congénitos orofaciales y de las extremidades1 . La secuencia de Poland (OMIM 173800) se caracteriza por la presencia de braquisindactilia unilateral y aplasia ipsolateral de la porción esternocostal del músculo pectoral mayor. Algunas veces se denomina síndrome de Poland por ser inicialmente descrito por Poland2 . Figure 1: Bilateral VI nerve palsy, resulting in Figure 2:La Picture showing left facial del palsy. síndrome Figure deformityyandPoland abnormalities of the combinación de3: Chest Moebius complete loss of abduction. right hand. se presenta raramente y se ha estimado una prevalencia de 1 en 500.000; en la literatura revisada no se cosmetic purposes. If the infant has feeding difficulties, recessive and x-linked recessive modes of inheritances. encontró esta physical asociación expuestostherapy prenatalmente a Surgery anden occupational is required. In addition to the involvement of chromosome 13, other loci map to 3q21-q22 and 10q21.3-q22.1.2 misoprostol3 . can correct ophthalmological problems and smile Figura 1 Nótese fenotipo típico de síndrome de Moebiuscandebesíndrome done which includesy muscle presenta surgery un reporte de Moebius Poland transfer Clinical features of Mobius syndrome includes Se complete Poland, hipoplasia del pectoral con atelia y pie equinovaro. from the thigh to the corner of the mouth. Surgery is enpalsy un neonato or partial unilateral or bilateral facial nerve with expuesto prenatalmente a misoprostol. SÍNDROME DE MOEBIUS ALTERACIONES OROFACIALES • La base de la nariz ha sido descrita como amplia y más bien plana • Epicanto bilateral, hipertelorismo • Malformaciones del oído (generalmente bilateral y confinado al lóbulo) • Paladar ojival y úvula bífida Figure 3: Thickend lower lipm andicrogna.a, nose deviation to rightmalformaciones de dientes y • Microglosia, m icrostomia, Figure 1: mandíbula bduction and partially absent adduction Figure 2: Absent right foot Figure 3: Thickend lower lip and nose deviation to right Figure 5: Thickened lower lip and Bell’s phenomena SÍNDROME DE MOEBIUS DIAGNÓSTICO DIFERENCIAL • Primero excluir trauma del parto PARÁLISIS FACIAL CONGÉNITA HEREDITARIA • Síndrome poco frecuente de disfunción aislada del nervio facial que causa debilidad facial o parálisis • La mayor parte de los casos reportados con herencia AD • Considerada inicialmente dentro de un espectro de Sd. de Moebius (MBS2) , en la actualidad se considera una enHdad aparte • Clínica: Asimetría facial, ptosis y movimientos faciales disminuidos • Compromiso asimétrico, bilateral, par.cipación desigual de las tres ramas del nervio facial Alrashdi et al. A family with hereditary congenital facial paresis and a brief review of the literature. Clinical Dysmorphology 2010, 19:198–201 (a) Fig. 1 (a) (c) Fig. 2 (b) (b) (d) (c) (d) 200 Clinical Dysmorphology 2010, Vol 19 No 4 T2-weighted volume sequence. Axial image through the internal auditory canals (IAC) show markedly hypoplastic facial nerves in the T2-weighted volume Axial aimage through the internal anterosuperior quadrants of both IACs (longsequence. arrows). Note normal canals (IAC) markedly hypoplastic facial nerves in the calibre vestibular nerveauditory posteriorly in the leftshow IAC (short arrow). Fig. 4 anterosuperior quadrants of both IACs (long arrows). Note a normal calibre vestibular nerve posteriorly in the left IAC (short arrow). Fig. 3 Fig. 3 was normal. They in several relative and neurological i neurological disord in their family res of a Spanish family in 1943 by Carme Spanish family sho nucleus. Verzijl et al. (2005c hereditary congeni family. The brainst Sagittal oblique reformat image through the left IAC (internal auditory canal) (cerebellum to right of image) shows normal calibre cochlea (e) (f) family with autoso reformatwith image left IAC (internal auditory nerve anteroinferiorly inSagittal the IACoblique (short arrow), the through vestibularthe nerve was compared wit (cerebellum to right image) shows normal calibre cochlea lying behind, before itscanal) division into superior and of inferior nerves. The (e) (f) nerve isanteroinferiorly in the IACjust (short arrow), hypoplastic left facial nerve visible in cross-section above andwith the vestibular nerve and with that of p lying behind, its division into superior and inferior nerves. The slightly in front of the cochlea nervebefore (long arrow). authors observed hypoplastic left facial nerve is visible in cross-section just above and neurons in the fac slightly in front of the cochlea nerve (long arrow). small facial nerve He had excessive tearing from the left eye, which genital facial palsy improved with ageHe but had his eyelids remained during ranged between 28 excessive tearingopen from the left eye, which sleep. His right palpebral fissure the left. 8700 for controls. improved with was age larger but histhan eyelids remained open during He had normal eyesleep. movements and examination of was other or necrosis, neuro His right palpebral fissure larger than the left. sagittal T1-weighted scan shows the brainstem to have a cranial nerves wasMidline unremarkable. Hismovements ears were promipresent. There we He had normal eye and examination of other normal configuration without flattening of the pons. nent bilaterally and mild nerves plagiocephaly was noticed. His He ears were promiencephalon and cranial was unremarkable. had normal development and there was no concern about cospinal tracts wer nent bilaterally and mild plagiocephaly was noticed. He his hearing nor speech. His peripheral blood karyotype syndrome is part o had normal development and there was no concern about diagnosis congenital facial weakness FISH for ao22q11 deletionnor were normal. Alrashdi et al. A family with hereditary congenital facial paresis and aand brief review f tdifferential he lhearing iterature. Clinical Dof ysmorphology 010, 1karyotype 9:198–201 of the posterior his speech. His peripheral 2blood PARÁLISIS FACIAL CONGÉNITA HEREDITARIA • Se propone que sería resultado de una alteración en el desarrollo del núcleo facial y/o del nervio • Con mayor frecuencia se asocia con ausencia total o parcial del nervio facial, ya sea unilateral o bilateral • Van der Wiel (1957) à Describe a una familia con la condición manifiesta en seis generaciones con 14 padres afectados y 32 niños afectados de un total de 70 • Ninguno de los hermanos afectados mostraba otros síntomas neurológicos • El autor sugiere que la enfermedad debe ser considerada como una forma monosintomá.ca del síndrome de Moebius Van der Wiel HJ (1957). Hereditary congenital facial paralysis. Acta Genet Sta.st Med 7:348. The neuropathology of hereditary congenital facial palsy vs Möbius syndrome H.T.F.M. Verzijl, MD; B. van der Zwaag; M. Lammens, MD, PhD; H.J. ten Donkelaar, MD, PhD; and G.W. Padberg, MD, PhD NEUROLOGY 64 February (2 of 2) 2005 Abstract—Objective: To characterize the neuropathology of hereditary congenital facial palsy. Methods: The authors compared n brainstem pathology of three members of one family f with autosomal dominant congenital facial palsy to e that • Estudio europatológico de parálisis acial congénita hereditaria n in three age-matched controls. The neuropathologic findings of the familial patients were compared with those of patients with Möbius syndrome. The authorsfobserved a marked decrease in the number of neurons in the facial motor varios casos de uResults: na m isma amilia nucleus with corresponding small facial nerve remnants. In the patients with congenital facial palsy the number of facial motoneurons ranged between 280 and 1,680 as compared to 5,030 and 8,700 for controls. No signs of neuronal degenera• 3 m iembros con parálisis facial congénita con There herencia AD se comparó tion or necrosis with neuronal loss, gliosis, or calcifications were present. were no other abnormalities of the rhombencephalon and its associated structures. The corticospinal tracts were fully developed. In contrast, Möbius syncon la d 3 ofcaontroles e la manomaly isma ofethe dad y con a dhypoplasia e los pofacientes con SM drome is e part more complexd congenital posterior fossa lwith the entire brainstem, including the traversing long tracts, with signs of neuronal degeneration and other congenital brain abnormalities. Neuropathologic findings confirm observations hereditary congenital facial fpalsy and Möbius • En Conclusion: los pacientes con PFC, el nclinical úmero de nthat euronas motoras aciales osciló syndrome are two different entities with a different pathogenesis. entre 280 y 1.680 en comparación con 5.030 y 8.700 para los controles. • Sin Insignos de dreported egeneración euronal patients o necrosis, érdida neuronal, congenital p unilateral facial nerve palsy has 1888, Möbius patients with n congenital been described as part of a wider syndrome on chrononprogressive bilateral facial and abducens nerve gliosis alcificaciones. Sin osyndrome tras anomalías del The rombencéfalo. mosome 22q11. palsy. o A c clear delineation of the Möbius pathogenesis of Möbius synNEUROLOGY 2005;64:649 –653 1 has been hampered by varying definitions. Isolated congenital facial palsy and the extended phenotype of congenital facial palsy with ocular muscle weakness, with or without craniofacial dysmorphisms and congenital abnormalities of the extremities, were criteria for the diagnosis of Möbius syndrome.2 Recently, we suggested facial palsy with impairment of ocular abduction as the primary criterion for Möbius syndrome.3 While dysfunction of other cranial nerves, orofacial malformations, limb malformations, and musculoskeletal system defects are associated features, we did not consider them.3 By restricting the definition, we excluded congenital facial palsy, and ascertained on clinical grounds that congenital facial palsy is a separate entity. 6 drome is unclear as hereditary cases are rare and most cases are sporadic.3 Two explanations have been proposed: a primary genetic7,8 and a primary ischemic cause.9-11 Teratogenicity has been suggested as an important environmental possibly secondary factor in both explanations.12 The postulated pathogenetic mechanisms in Möbius syndrome are based on limited pathologic observations.13 Previously, we suggested, on clinical grounds, that Möbius syndrome is more than a cranial nerve or nuclear developmental disorder and that it could be viewed as a rhombencephalic developmental disorder with variable severity, involving motor nuclei and axons, as well as traversing long tracts.3 To investigate the hypothesis that hereditary con- • En contraste, el síndrome de Moebius es parte de una anomalía congénita más compleja de la fosa posterior con hipoplasia del tronco cerebral. Se asocia con degeneración neuronal y otras anomalías cerebrales congénitas PARÁLISIS FACIAL CONGÉNITA HEREDITARIA GenéHca: • En una gran familia holandesa con parálisis facial congénita, Kremer et al. (1996) iden.ficaron un locus candidato en el cromosoma 3q21-‐q22 • Michielse et al. (2006): análisis en una familia paquistaní con parálisis facial congénita dominante • Una región cosegregante con el trastorno fue iden.ficada en el brazo largo del cromosoma 3q21-‐q22 • Mediante el uso de ARN de hibridación in situ, Van der Zwaag et al. (2005) iden.ficaron varios genes candidatos dentro de la región crí.ca • Estudio de mutaciones en siete genes (KLF15, CCDC37, PODXL2, TMCC1, PLXNA1, PLXND1 y GATA2), no detectadas Alrashdi et al. A family with hereditary congenital facial paresis and a brief review of the literature. Clinical Dysmorphology 2010, 19:198–201 Volume 24 # Number 5 # September 2013 1040-8738 ! 2013 Wolters Kluwer Health | Lippincott 400 www.co-ophthalmology.com Volume 24 W # TUBB3 syndrome TUBB3-CFEOM CFEOM1B or 3A ass neurological symp TUBB3-E410K-syndrome TUBB3-E410KCFEOM CFEOM associated w features. Arises fro acid substitution PARÁLISIS FACIAL CONGÉNITA HEREDITARIA TUBB2B 6p25.2 TUBB2B-E421K-Congenital fibrosis of the extraocular muscles a Table 1. Genetic classification of currently CCDDs !!! 13q12.11 recognized Congenital fibrosis of the extraocular muscles type 3C TUBB2B-E421KCFEOM !!! AD Three affected memb rare TUBB2B phen CFEOM only occu acid substitution CFEOM3C 609384 AD Four affected membe 609428 MIM AR Inheritance Six affected members Comments same family Phenotype Main category Gene Locus Tukel syndrome Phenotype CFEOM-U abbreviation Duane retraction Other horizontal syndrome !!! !!! Isolated Duane retraction Moebius syndrome syndrome MBS 157900 !!! Unknown Prevalence all casesofof0.0002 incom bilateral 14–2 births; rareinchromo SALL4 20q13.2 Duane-radial ray syndrome Rare 23 recognized mutat gaze disorders !!! Prevalence "0.1%; 8q12–13 DRRS HGPPS 607323 607313 AD AR CHN1 2q31.1 Duane retraction syndrome 2 DURS2 604356 AD Rare; 10 recognized !!! Possible X chrm Wildervanck syndrome Wildervanck 314600 Unknown Females>>males 7p15.2 Bosley-Salih-Alorainy syndrome BSAS 601536 AR Rare Athabascan brainstem dysgenesis Hereditary syndrome congenital facial ABDS Multiple chrm locations paresis 1 DRS Chromosomal Chromosomal DRS 12q12 17q21.3 Congenital of thefacial Hereditaryfibrosis congenital extraocular muscles type 1A !!! HOXA1 !!! !!! !!! Congential fibrosis of the extraocular muscles Unknown Horizontal gaze palsy and Duane retraction syndrome 1 progressive scoliosis !!! Other facial motility disorders DRS 11q24.2 ROBO3 Other vertical gaze disorders !!! KIF21A HOXB1 !!! 3q21-q22 10q21.3-q22.1 Isolated superior oblique palsy DURS1 Isolated SOP HCFP1 126800 ——— AD 601471 Three unrelated pati Unknown AD !!! PHOX2A 1p34.1-p32 Xq24-q27.1 11q13 Rare !!! !!! Unilateral or bilatera a wide spectrum Rare developmental ab (excluding syndro CFEOM1A HCFP3 135700 614744 AD AR 13 recognized muta Four affected in heterogeneity res unrelated fam phenotypes (CFEO Hereditaryfibrosis congenital Congenital of theptosis 1 extraocular muscles type 3B PTOS13B CFEOM 178300 AD Congenital fibrosis of the extraocular muscles type 2 CFEOM 2 Hereditary congenital facial paresis 2 HCFP2 604185 AD paresis 3 !!! Several familial Hereditary congenital ptosis 2 PTOS2 300245 602078 AR X-linked TUBB3 16q24.3 fibrosis of the CFEOM3A 600638 AD AD, autosomal dominant; AR, autosomal recessive; chrm, chromosome;Congenital HCFP, Hereditary congenital facial paresis; MIM, Online Mendelian Inheritance of Man number. extraocular muscles type 3A a CCDD, congenital cranial dysinnervation disorder. Rare Linkage in one Five currently recogn TUBB3 mutations res phenotypic hetero recognized mutat either in isolation as part of a large to as TUBB3 synd Congenital fibrosis of the extraocular muscles type 1B CFEOM1B TUBB3 syndrome TUBB3-CFEOM CFEOM1B or 3A as neurological sym TUBB3-E410K-syndrome TUBB3-E410K- CFEOM associated features. Arises fr acid substitution Bosley TM, Abu-‐Amero KK, Oystreck DT. Congenital cranial dysinnerva.on disorders: a concept CFEOM in evolu.on. Curr Opin Ophthalmol. 2013 Sep; 24(5):398-‐406. SÍNDROME DE MOEBIUS ESTUDIO • No hay estudios de laboratorio con hallazgos específicos para el síndrome de Moebius • Neuroimágenes recomendadas • EMG se puede u.lizar para ayudar a determinar si los síntomas del paciente se derivan de trauma del nacimiento • Hallazgos histológicos gruesos incluyen la asimetría de la médula, pero la apariencia externa del cerebro generalmente es normal (Figs 1A, 1B). Discussion drome [6-19]. Although the pathogenesis of Möbius syndrome is incompletely understood, four mechanisms have been proposed: (1) hypoplasia of cranial nerve nuclei, (2) necrosis of brainstem nuclei, (3) peripheral neuropathies, and (4) myopathies [18]. During the first trimester, the developing brainstem typically responds to injury with malformative changes, such as cranial nerve hypoplasia. Reactive necrosis and SÍNDROME DE MOEBIUS Our patients demonstrated typical features of Möbius syndrome. All manifested bilateral incomplete facial palsy, and all had involvement of the sixth cranial nerve [4]. Two of the seven manifested talipes equinovarus, NEUROIMÁGENES • TC o RM cerebral pueden demostrar calcificaciones bilaterales en las regiones de los núcleos PC VI • Sin embargo, estas calcificaciones no son específicas para la enfermedad • El tronco encefálico puede aparecer hipoplásico, con aplanamiento del piso del 4º ventrículo Figure 1. (A) Computed tomographic scans illustrating the typical appearance of brainstem calcification at the level of the pons in 5/7 children with Möbius syndrome. (B) The scans from the same patient indicating no evolution over a 4-year interval. 40 PEDIATRIC NEUROLOGY Vol. 30 No. 1 Dooley JM, Stewart WA, Hayden JD, Therrien A. Brainstem calcifica.on in Möbius syndrome. Pediatr Neurol. Jan 2004;30(1):39-‐41. SÍNDROME DE MOEBIUS Ferreira et al Topic in Magnetic Resonance Imaging & Volume 22, Number 6, December 2011 FIGURE 4. Midsagittal T1-weighted MRI scan shows flattening of the ventral pons and a dorsal vault projection from the pontine tegmentum into the fourth ventricle. The vermis is hypoplastic. Axial T2-weighted MRI scan demonstrates hypoplasia of middle cerebellar peduncles. Axial 3D-CISS MRI scan with normal abducens nerves, but lacking seventh and eighth right cranial nerves. Courtesy of Ronnie Peterson Alves, MD, Porto Alegre, Brazil. In a group of 37 Dutch Möbius patients of different age Further analysis by diffusion tensor imaging (DTI) with 16,21 groups,22 the majority of patients presented a homogeneous color coding and fiber tracking demonstrates also striking findings: an abnormal bundle of transversely oriented fibers clinical picture characterized by facial diplegia of the upper and forming the typical pontine tegmental cap as well as absence of lower facial muscles, bilateral abduction impairment, hypoglossia, decussation of the superior cerebellar peduncles and of the and craniofacial and limb malformations. The distribution of usual transverse fibers in the ventral pons. the facial in the RMbS casesImaging, contrasts considerably with6, that Mar.ns R, et al. Imaging Findings in Congenital Cranial Dysinnerva.on Disorders. Topic palsy in Magne.c esonance Volume 22, Number Although found in the common supranuclear and infranuclear types of December 2011. cases of MbS may present with abnormalities in Topic in Magnetic Resonance Imaging & S M Volume 22, Number 6,D December 2011 ÍNDROME E OEBIUS Congenital Cranial Dysinnervation Disorders FIGURE 5. A 5-year-old with congenital right facial palsy and impairment of ocular abduction. Sagittal and axial 3D-CISS MRI scans demonstrate straightening of the floor of fourth ventricle because of lacking right facial colliculi (arrowhead). Abducens nerves (arrows) and right seventh and eighth cranial nerves are absent. Summary Imaging Findings MbS B. Unilateral or bilateral absence of facial nerve A. Straightening of the floor of fourth ventricle due to absence Absence of hypoglossal Mar.ns R, et al. Imaging Findings in Congenital Cranial Dysinnerva.on Disorders. TC. opic in Magne.c Resonance Ieminence maging, Volume 22, Number 6, facial colliculi ventricle D. Variable lacking sixth, eighth, ninth, and 12th cranial nerves December 2of 011. SÍNDROME DE MOEBIUS MANEJO • No hay un tratamiento definiHvo disponible • Manejo sintomáHco de complicaciones, enfoque mul.disciplinario: • • • • • • Úlceras o abrasiones corneales Férulas, prótesis O..s media Vigilancia de infecciones respiratorias Alteraciones de la deglución Apoyo psicológico familiar • Tratamiento ortopédico y/o quirúrgico del pie bot • Se recomienda postergar la cirugía para el estrabismo porque la condición a menudo mejora con la edad SÍNDROME DE MOEBIUS INJERTO Y PROCEDIMIENTOS DE REINERVACIÓN • Las regiones afectadas no .enen un sistema neuromuscular funcional à El injerto de nervio y las técnicas de susHtución de los NC han tenido poco éxito • Sin embargo, los procedimientos que implicarían la integración de un nuevo sistema neuromuscular podrían tener éxito • La restauración de la función puede ser más exitosa si la cirugía se lleva a cabo antes de los 7 años de edad • Técnicas u.lizadas: • Uso del nervio accesorio no afectado o la rama mesentérica del PC V como donantes para los procedimientos de reinervación • Disposi.vos compuestos de trasplantes musculares y tendinosos, junto con procedimientos de reinervación • Transferencia muscular de Gracilis con la inervación del nervio masetero HOSPITAL CLÍNICO SAN BORJA ARRIARÁN SERVICIO DE NEUROPSIQUIATRÍA INFANTIL SÍNDROME DE MOEBIUS Dr. Guillermo Fariña Kutz Neurólogo Infan.l Dra. Daniela CasHllo Villagrán Residente Neurología Infan.l Mayo 2014