HOSPITALC LÍNICOS ANB ORJAA RRIARÁN SERVICIO DEN ... · SÍNDROME)DE)MOEBIUS) HOSPITALC LÍNICOS ANB ORJAA RRIARÁN) SERVICIO)DEN EUROPSIQUIATRÍAI NFANTIL! Dr.GuillermoFariñaKutz

SNDROME DE MOEBIUS

HOSPITAL CLNICO SAN BORJA ARRIARN SERVICIO DE NEUROPSIQUIATRA INFANTIL

Dr. Guillermo Faria Kutz Dra. Daniela CasHllo Villagrn Neurlogo Infan.l Residente Neurologa Infan.l

Mayo 2014

DEFINICIN

Se debe, en parte, a la prdida de la funcin de nervios craneales motores

La mayora de los casos se diagnos.can durante la infancia

Es una enfermedad no progresiva talipes equinovarus, syndactyly, hemimelia, Polandsanomaly, craniofacial deformities, etc. (Figures 3 and 4).

Hemifacial microsomia (HFM)

A common association is Hemifacial Microsomia (HFM), anumbrella term that covers a variety of developmentaldefects. HFM involves first and second branchial archderivatives with a highly variable phenotype. Deformitiesmay include auricular defects, preauricular tags andfistulae, microtia-atresia, mandibular, maxillary, andorbital hypoplasia, micropthalmia, epibulbar dermoid,strabismus, conductive or sensoneural hearing loss, andhypoplastic facial muscles27 (Figure 5a and b).

OMENS and the expanded OMENS-Plus classifications arethe most widely acceptable systems of describing thecraniofacial and extracranial anomalies of HFM.28,29

Goldenhar syndrome, which often shows additionaldefects of vertebrae, heart, and kidneys, is included. Gorlinet al.30 suggested the term oculoauriculovertebral dysplasia(OAVS) for this disorder. The phenotypic characteristics ofOAVS and variants have been analyzed recently.27,31,32

Facial palsy has been reported to occur in 22%e50% ofpatients with HFM.33e36 The observations of anatomicvariables of HFM are supported by the pathogenic theory ofaxial mesodermal dysplasia.35e39 Findings from a recentongoing case e control study40 are consistent with the

vascular disruption hypothesis. However, links betweenHFM risk and other pathogenetic processes such as oxygenfree radical generation,41,42 maternal diabetes,43 or expo-sure to teratogens39 and finally, assisted reproductivetechnologies have been postulated by many authors.44e46

Neonatal asymmetric crying faces (ACF)

The clinical hallmark of this condition is a symmetricappearance at rest, but significant unilateral depression ofthe lower lip with crying (Figure 6). A variety of terms havebeen used to characterize the dysfunction as: asymmetriccrying faces, congenital hypoplasia of the depressor angulioris muscle, or developmental unilateral lower lip palsy.Pape and Pickering named the phenotype ACF in 1972.47

Cayler first described the association of ACF withcongenital cardiac disease, and subsequently named itcardiofacial syndrome.48 The cause is either facial nervecompression or faulty muscle and/or nerve development.

Approximately 10% of developmental cases have associ-ated major malformations, and cardiac anomalies, whichshould provoke an evaluation for cardiofacial syndrome.49,50

Many of these patients have the 22q11.2 deletion. Furtherinvestigation for other anomalies is indicated in selectedcases with no signs of improvement by obtaining a FISH(Fluorescence in situ hybridization) analysis for a chro-mosomal microdeletion of 22q11.2.

Figure 2 Example of classical Mobius syndrome case. Preoperative picture of a 9-year old boy with bilateral developmental facialpalsy (Mobius syndrome), left side more involved than the right. Note the absence of expression and the mask-like face appearance(Figure 2a). Neurological examination in addition to the bilateral seventh nerve involvement (L > R), revealed deficits to the third(III) bilaterally, (inability to gaze upward), bilateral sixth (VI) (paralysis of lateral gaze) and twelve cranial nerves (XII). He hadundergone a left otoplasty for correction of prominent ear deformity and a static fascial sling procedure to his left commissure,performed elsewhere at a younger age. He was treated with a two-stage free gracilis muscle to the left cheek neurotized frommotor fibers from the contralateral facial nerve. Secondary revisional surgery took place two years later that included a mini-temporalis pedicle transfer to the left commissure. Appearance of the patient in his last follow-up two years after the secondarysurgery (Figure 2b).

Developmental facial paralysis 1321

DEBILIDAD FACIAL CONGNITA ASOCIADA A ALTERACIN EN LA ABDUCCIN OCULAR

talipes equinovarus, syndactyly, hemimelia, Polandsanomaly, craniofacial deformities, etc. (Figures 3 and 4).

Hemifacial microsomia (HFM)

A common association is Hemifacial Microsomia (HFM), anumbrella term that covers a variety of developmentaldefects. HFM involves first and second branchial archderivatives with a highly variable phenotype. Deformitiesmay include auricular defects, preauricular tags andfistulae, microtia-atresia, mandibular, maxillary, andorbital hypoplasia, micropthalmia, epibulbar dermoid,strabismus, conductive or sensoneural hearing loss, andhypoplastic facial muscles27 (Figure 5a and b).

OMENS and the expanded OMENS-Plus classifications arethe most widely acceptable systems of describing thecraniofacial and extracranial anomalies of HFM.28,29

Goldenhar syndrome, which often shows additionaldefects of vertebrae, heart, and kidneys, is included. Gorlinet al.30 suggested the term oculoauriculovertebral dysplasia(OAVS) for this disorder. The phenotypic characteristics ofOAVS and variants have been analyzed recently.27,31,32

Facial palsy has been reported to occur in 22%e50% ofpatients with HFM.33e36 The observations of anatomicvariables of HFM are supported by the pathogenic theory ofaxial mesodermal dysplasia.35e39 Findings from a recentongoing case e control study40 are consistent with the

vascular disruption hypothesis. However, links betweenHFM risk and other pathogenetic processes such as oxygenfree radical generation,41,42 maternal diabetes,43 or expo-sure to teratogens39 and finally, assisted reproductivetechnologies have been postulated by many authors.44e46

Neonatal asymmetric crying faces (ACF)

The clinical hallmark of this condition is a symmetricappearance at rest, but significant unilateral depression ofthe lower lip with crying (Figure 6). A variety of terms havebeen used to characterize the dysfunction as: asymmetriccrying faces, congenital hypoplasia of the depressor angulioris muscle, or developmental unilateral lower lip palsy.Pape and Pickering named the phenotype ACF in 1972.47

Cayler first described the association of ACF withcongenital cardiac disease, and subsequently named itcardiofacial syndrome.48 The cause is either facial nervecompression or faulty muscle and/or nerve development.

Approximately 10% of developmental cases have associ-ated major malformations, and cardiac anomalies, whichshould provoke an evaluation for cardiofacial syndrome.49,50

Many of these patients have the 22q11.2 deletion. Furtherinvestigation for other anomalies is indicated in selectedcases with no signs of improvement by obtaining a FISH(Fluorescence in situ hybridization) analysis for a chro-mosomal microdeletion of 22q11.2.

Figure 2 Example of classical Mobius syndrome case. Preoperative picture of a 9-year old boy with bilateral developmental facialpalsy (Mobius syndrome), left side more involved than the right. Note the absence of expression and the mask-like face appearance(Figure 2a). Neurological examination in addition to the bilateral seventh nerve involvement (L > R), revealed deficits to the third(III) bilaterally, (inability to gaze upward), bilateral sixth (VI) (paralysis of lateral gaze) and twelve cranial nerves (XII). He hadundergone a left otoplasty for correction of prominent ear deformity and a static fascial sling procedure to his left commissure,performed elsewhere at a younger age. He was treated with a two-stage free gracilis muscle to the left cheek neurotized frommotor fibers from the contralateral facial nerve. Secondary revisional surgery took place two years later that included a mini-temporalis pedicle transfer to the left commissure. Appearance of the patient in his last follow-up two years after the secondarysurgery (Figure 2b).

Developmental facial paralysis 1321

SNDROME DE MOEBIUS

HISTORIA

1880 Von Graefe describe un caso de dipleja facial congnita

1888 y 1892

El sndrome es descrito con ms detalle por Paul Julius Mbius, neurlogo alemn

Von Graefe y Mbius aceptaron slo casos con DIPLEJA FACIAL CONGNITA Y PARLISIS DEL VI P.C. BILATERAL para consHtuir el sndrome de Moebius

Leipzig, W Engelman. 1880;6:60.

Munchen Medizinische Wochenschri7. 1888;35:91-4. Munchen Medizinische Wochenschri7. 1892;39:17-21, 41-3, 55-8.

SNDROME DE MOEBIUS

HISTORIA

En la actualidad, la definicin y criterios diagnsHcos varan entre autores

Algunos ms restric.vos en su definicin, requieren la presencia de una anomala congnita musculoesquelHca para hacer el diagns.co

1939 Henderson ampla la definicin e incluye casos con parlisis facial congnita UNILATERAL

381

THE CONGENITAL FACIAL DIPLEGIA SYNDROME: -CLINICAL FEATURES, PATHOLOGY AND ETIOLOGY.1

A REVIEW OF SIXTY-ONE CASES

BY J. L. HENDERSON(From the Department of Child Life and Health, University of Edinburgh.)

CONGENITAL paralysis of cranial nerves is sufficiently rare to attractspecial attention. The ocular and facial nerves are those most frequentlyaffected and the anatomical relationships of the latter render them suscep-tible to paralysis from a greater variety of causes. Thus, there are severaltypes of congenital facial palsy. The intra-partum types predominate and,with the extremely rare exception of bilateral peripheral trauma, they areall unilateral. Of the ante-partum types, however, the bilateral variety isthe commonest and is usually associated with other cranial nerve palsies.This paper is solely concerned with the ante-partum bilateral type.

A child displaying many typical features of the condition was seenrecently at the Royal Edinburgh Hospital for Sick Children. Perusal ofthe relevant literature showed that no adequate review of the publishedcases had ever been undertaken ; German literature proved to be the mostfruitful, while British literature contained brief accounts of only six cases.An analysis of the clinical and other features of this remarkable congenitalsyndrome may, therefore, be of interest.

CASE REPORT.E. O., female, aged 1 year 10 months.History.The parents, a sister aged 12 and a brother aged 8, are healthy. The

pregnancy was normal. Spontaneous delivery followed an uneventful labour lastingnine hours. The birth weight was about eight pounds. A peculiar facial appearance,bilateral convergent strabismus and club-foot were all noticed shortly after birthby the doctor in attendance. The baby apparently nursed quite well, althoughher mother maintains that she did not nurse as well as her other children. She wasweaned when two months old. There was never any dysphagia nor nasalregurgitation.

The patient first came under observation at the age of 5 months, her mothercomplaining that she had never smiled nor moved her faceeven when laughingand crying. During the first few weeks she thought the infant had a film over

1 Based upon a thesis accepted for the degree of M.D.Edin., July, 1938.

at University of M

anchester on May 15, 2014

http://brain.oxfordjournals.org/D

ownloaded from

Brain. 1939;62:381-403.

SNDROME DE MOEBIUS

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

CURRENTOPINION Congenital cranial dysinnervation disorders:a concept in evolution

Thomas M. Bosleya, Khaled K. Abu-Ameroa,b, and Darren T. Oystrecka,c

Purpose of reviewWe review the congenital and genetic diagnoses that are currently included in the congenital cranialdysinnervation disorders (CCDDs).

Recent findingsRecent 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 beenidentified, permitting a better understanding of associated phenotypes. More information is availableregarding neurodevelopmental and clinical effects of various gene mutations associated with individualCCDDs. For certain CCDDs, the phenotype of a particular individual may not completely predict thegenotype, and conversely, the genotype may not always predict the phenotype.

SummaryThe CCDD concept has focused attention on specific congenital disturbances of human ocular motilityand on the fact that these disorders are typically neurogenic in origin. The past decade has seen rapidevolution 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 genotypephenotype correlations in the future.

Keywordsbrainstem development, congenital cranial dysinnervation disorders, cranial nerves, ocular motility, strabismus

INTRODUCTIONOphthalmologists recognized over 60 years ago thatcertain children were born with congenital ocularmotility abnormalities associated with restrictedeye movements and fibrotic extraocular muscles[1]. This observation led to the assumption thatthe primary problem was a congenital abnormalityof muscle development and thus to the conceptof congenital fibrosis of the extraocular muscles(CFEOM) [2]. Duane retraction syndrome (DRS) [3]and Moebius syndrome (MBS) [4] were recognizedearly on, and a number of other sporadic andfamilial congenital ocular motility syndromes wereadded as time passed.

Evidence accumulated over time that mostor all of these syndromes had a neurogenic cause.Therefore, in 2002 an alternative concept ofcongenital cranial dysinnervation disorders(CCDD) was proposed that shifted the focus awayfrom muscle development [5]. Developments inthe last decade have supported the CCDD concept,with all currently identified genes that cause CCDDswhen mutated affecting brainstem and/or cranial

nerve development. It is likely that we have not yetidentified all syndromes that would fall under theCCDD rubric, although presumably the ones not yetidentified are less common (or at least harder tocharacterize) than those already recognized.

THE CONGENITAL CRANIALDYSINNERVATION DISORDERS CONCEPTThe CCDD concept encompasses most congenital,static abnormalities of ocular motility and someadditional abnormalities primarily involving lid

aDepartment of Ophthalmology, College of Medicine, King Saud Uni-versity, Riyadh, Saudi Arabia, bDepartment of Ophthalmology, College ofMedicine, University of Florida, Jacksonville, Florida, USA and cDivision ofOphthalmology, Faculty of Health Sciences, University of Stellenbosch,Tygerberg, South Africa

Correspondence to Dr Thomas M. Bosley, MD, King Abdulaziz UniversityHospital, PO Box 245, Riyadh 11411, Saudi Arabia. Tel: +966567869479; fax: +966 1 4775724; e-mail: [email protected]

Curr Opin Ophthalmol 2013, 24:398406

DOI:10.1097/ICU.0b013e3283645ad6

www.co-ophthalmology.com Volume 24 ! Number 5 ! September 2013

REVIEW

Curr Opin Ophthalmol. 2013 Sep;24(5):398-406.

Hace ms de 60 aos Ciertos nios nacen con alt. de la mo.lidad ocular asociados a msculos extraoculares fibr.cos

Concepto de fibrosis congnita de los msculos

extraoculares (CFEOM)

Sndrome de retraccin de Duane (DRS) y el sndrome de Moebius (MBS) fueron reconocidos como patologas nicas desde un principio

DESRDENES DE DESINERVACIN CRANEAL CONGNITA La evidencia acumulada muestra que la mayor parte de estos sndromes tendran una causa neurognica

2002 concepto alternaHvo de DESRDENES DE DESINERVACIN CRANEAL CONGNITA (CCDD) que cambi el enfoque del desarrollo muscular

Los avances en la l.ma dcada han apoyado el concepto de CCDD, con todos los genes iden.ficados hasta el momento afectaran el desarrollo del tronco cerebral y/o PC

Es probable que an no se hayan iden.ficado todos los sndromes 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.

Copyright

Lippincott William

s & Wilkins. U

nauthorized reproduction of this article is prohibited.

Table 1. Genetic classification of currently recognized CCDDsa

Main category Gene Locus PhenotypePhenotypeabbreviation MIM Inheritance Comments

Duane retractionsyndrome

!!! !!! Isolated Duane retractionsyndrome

DRS !!! Unknown Prevalence "0.1%; accounts for 15% ofall cases of incomitant strabismus;bilateral in 1420%

SALL4 20q13.2 Duane-radial ray syndrome DRRS 607323 AD Rare

!!! 8q1213 Duane retraction syndrome 1 DURS1 126800 AD Three unrelated patients

CHN1 2q31.1 Duane retraction syndrome 2 DURS2 604356 AD Rare; 10 recognized mutations

!!! Possible X chrm Wildervanck syndrome Wildervanck 314600 Unknown Females>>males

HOXA1 7p15.2 Bosley-Salih-Alorainy syndrome BSAS 601536 AR Rare

Athabascan brainstem dysgenesissyndrome

ABDS

!!! Multiple chrmlocations

Chromosomal DRS Chromosomal DRS !!! !!! Unilateral or bilateral DRS associated witha wide spectrum of otherdevelopmental abnormalities(excluding syndromes above)

Congential fibrosisof the extraocularmuscles

KIF21A 12q12 Congenital fibrosis of theextraocular muscles type 1A

CFEOM1A 135700 AD 13 recognized mutations; clinicalheterogeneity resulting in differentphenotypes (CFEOM1A>CFEOM3B)

Congenital fibrosis of theextraocular muscles type 3B

CFEOM 3B

PHOX2A 11q13 Congenital fibrosis of theextraocular muscles type 2

CFEOM 2 602078 AR Five currently recognized mutations

TUBB3 16q24.3 Congenital fibrosis of theextraocular muscles type 3A

CFEOM3A 600638 AD TUBB3 mutations result in allelicphenotypic heterogeneity; 8/14recognized mutations result in CFEOMeither in isolation (CFEOM1B or 3A) oras part of a larger syndrome referredto as TUBB3 syndrome


CFEOM1B

TUBB3 syndrome TUBB3-CFEOM CFEOM1B or 3A associated withneurological symptoms

TUBB3-E410K-syndrome TUBB3-E410K-CFEOM

CFEOM associated with neurologicalfeatures. Arises from an E410K aminoacid substitution

TUBB2B 6p25.2 TUBB2B-E421K-Congenitalfibrosis of the extraocularmuscles

TUBB2B-E421K-CFEOM

!!! AD Three affected members in same family;rare TUBB2B phenotype whereCFEOM only occurs with E421K aminoacid substitution

!!! 13q12.11 Congenital fibrosis of theextraocular muscles type 3C

CFEOM3C 609384 AD Four affected members in same family

Tukel syndrome CFEOM-U 609428 AR Six affected members in three sibships ofsame family

Other horizontalgaze disorders

!!! !!! Moebius syndrome MBS 157900 Unknown Prevalence of 0.0002% to 0.002% ofbirths; rare chromosomal etiology

ROBO3 11q24.2 Horizontal gaze palsy andprogressive scoliosis

HGPPS 607313 AR 23 recognized mutations

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weakn

ess

with

limite

dab

du

ctio

n.Patie

nts

with

MB

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qu

en

tlyh

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[11]

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to

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2].

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an

dp

rogre

ssive

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invo

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co

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the

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gen

e,

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vo

lved

ind

ecu

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no

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ind

evelo

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eu

ral

tracts

inth

eb

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tra

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al

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lasia

with

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ue

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op

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4]

an

dfa

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en

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istinct

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en

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To

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sh

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tified

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gh

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7]

bu

tn

ot

all

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ilies.

Otherfacialmotility

disorders

Th

isgro

up

of

diso

rders

inclu

des

co

ngen

ital

no

n-

trau

matic

facia

lw

eakn

ess

iniso

latio

no

ro

ccasio

n-

ally

inasso

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with

co

mita

nt

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late

db

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ral

co

ngen

ital

pto

sisis

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ded

.T

hu

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uta

tion

sin

on

lyo

ne

gen

e,

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1,

have

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fau

to-

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al

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cia

lp

als

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asu

bset

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[18

&&].

Congenita

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ndisorders

genetic

mechanisms

So

me

CC

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ary

ab

no

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so

fb

rain

stem

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pm

en

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wh

ich

the

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cle

io

fo

cu

lar

mo

tor

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es

do

no

td

evelo

pco

rrectly

(e.g

.,th

eH

OX

A1

spectru

man

dC

FEO

M2).

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ers

invo

lve

ab

no

rmalitie

so

faxo

nal

gu

idan

ce

resu

lting

inab

no

rmal

low

er

mo

tor

neu

ron

inn

erv

atio

no

fo

rbita

lm

usc

les

(e.g

.,C

FEO

M1

an

dC

FEO

M3),

an

dat

times

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dro

mic

featu

res

(e.g

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mu

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Other vertical gazedisorders

!!! !!! Isolated superior oblique palsy Isolated SOP Unknown Several familial reports

Other facial motilitydisorders

!!! 3q21-q22 Hereditary congenital facialparesis 1

HCFP1 601471 AD Rare

!!! 10q21.3-q22.1 Hereditary congenital facialparesis 2

HCFP2 604185 AD Rare

HOXB1 17q21.3 Hereditary congenital facialparesis 3

HCFP3 614744 AR Four affected individuals from twounrelated families

!!! 1p34.1-p32 Hereditary congenital ptosis 1 PTOS1 178300 AD Rare

!!! Xq24-q27.1 Hereditary congenital ptosis 2 PTOS2 300245 X-linked Linkage in one family

AD, autosomal dominant; AR, autosomal recessive; chrm, chromosome; HCFP, Hereditary congenital facial paresis; MIM, Online Mendelian Inheritance of Man number.aCCDD, congenital cranial dysinnervation disorder.

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Falta de abduccin, con limitacin de la aduccin, retraccin variable del globo ocular y estrechamiento de la hendidura palpebral en aduccin

Espordico, unilateral o bilateral, aislado o sindrom.co Gen HOXA1 (creacin o supervivencia de neuronas PC VI) o genes CHN1, SALL4 (crecimiento de axones al recto lateral)

Sndrome de retraccin de

Duane

Alteracin de movimientos oculares horizontales y/o ver.cales, y ptosis

Unilateral o bilateral Estrabismo divergente y posicin anormal de la cabeza, en especial la elevacin del mentn

Fibrosis congnita de

msc. extraoculares

Parlisis de la mirada horizontal completa o parcial congnita, sin compromiso mirada ver.cal, escoliosis progresiva de inicio precoz

Gen ROBO3 (involucrado en la decusacin de tractos neurales en tronco enceflico).

Parlisis de la mirada

horizontal y escoliosis progresiva


sometimes with associated ocular motor abnormalities(congenital facial weakness and Mobius syndrome).

The investigators suggested that in addition to DRS andCFEOM, it is also possible that familial HGPPS and atleast some forms of Mobius syndrome result fromdevelopmental dysinnervation.40 Traboulsi41 suggestedthat CCDDs might involve cranial sensory as well asmotor nerves, Figure 5. Recently, Kolling et al42 indicatedcongenital Browns syndrome is caused by missingfourth cranial nerve in some cases, which put it in thecategory of congenital dysinnervation. This fits intoAssaf assertion that CID can occur in congenital non-progressive ocular motility disorders not explained bypurely isolated oculo-motor nerve palsy.38

The above description of CCDDs is more or less thesame as the CID described by Assaf a few years earlier.To CID the investigators of CCDDs added ptosis, Mobiussyndrome, and HGPPS. However, it is well known thatptosis is a feature of CFEOM (see definition of theCFEOM above) and Mobius syndrome has been knownto have neural aetiology for some time.34,35 Moreover, inhis original paper on the CID38 Assaf alluded to Mobiussyndrome, quoting it as supporting evidence for the CIDsyndrome. Additionally, the HGPPS is not a CCDD persay; it associated with scoliosis because of innervationaldisorder of the muscles of the spine. Thus, it is a caseof CID involving the ocular and spinal muscles.Furthermore, although the HGPPS is genetic it is progres-sive and associated with progressive ophthalmoplegiaand progressive scoliosis, which is against the definitionof CCDDs and are defined as non-progressive.

Therefore, CID and CCDDs syndromes are essentiallythe same. The term CID rather than CDDDs might bepreferable for the following reasons:

! This was the original description of the congenitaldysinnervation syndrome in 1998, several yearspreceding that of the CCDDs.

! CID may occur beyond the cranial motor nerves andmay occur in other parts of the body, thus a moregeneral and encompassing name of CID seems moreappropriate than CCDDs, which localise it to cranialnerves for no logical reason.

CID affects various cranial motor, and perhaps sensory,nerves resulting in a variety of clinical pictures. It mayalso affect motor and perhaps non-motor innervations inother parts of the body beyond the cranial nerves. Thedescription of the effects in such pathology is beyond thescope of an ophthalmologist.

Genetics of congenital strabismus

Congenital strabismus in humans can result frommutations in a number of genes, including PHOX2A,43

SALL444,45 HOXA146 ROB03,47 and KIF21A48 that areessential to the normal development of brainstem motorneurons or axons. The genetics of CID ocular motilitydefects affecting cranial nerves (CCDDs) have beenstudied extensively by various investigators particularlyDr Engel and collaborators at Harvard. These were foundto arise from mutations in any of the above of genes.The PHOX2A and KIF21A genes appear to affectdevelopment of the midbrain oculomotor and/ortrochlear axis, and mutations result in abnormalities ofboth vertical and horizontal gaze. On the other handSALL4, ROBO3, and HOXA1 affect development of thepontine abducens axis, and mutations result in primaryabnormalities of horizontal gaze. The underlying genedefects lead to errors at various developmental stage andlocations along the developing neuroaxis, includingpredicted errors in hindbrain segmentation (HOXA1),motoneuron specification (PHOX2A), and axon targeting(CFEOM1, ROBO3).49

Congenital fibrosis syndrome of the EOM

To date, three genetic CFEOMs loci have been identifiedand three clinical phenotypes have been delineated,CFEOM 13.

CFEOM1 has autosomal dominant inheritance withfull penetrance and minimal variation in expression hasbeen mapped to the centromeric region of chromosome12.5052 It has also now been demonstrated that CFEOMIresults from heterozygous mutations in the KIF21A geneencoding a kinesin motor protein.48

Figure 5 Clinical syndromes in CCDDs and correspondingcranial nerves. Responsible gene names are given in italics. Thethree lines and arrows in the bottom part of the illustrationindicate associations in individual case reports or minority ofpatients with known syndromes. All conditions listed in thisdiagram are congenital. *Mobius syndrome can also involvecranial nerves 9 and 12 (see Traboulsi).41

CID and CCDDsAA Assaf

1256

Eye

Assaf AA. Congenital innerva.on dysgenesis syndrome (CID)/ congenital cranial dysinnerva.on disorders (CCDDs). Eye (2011) 25, 12511261.

EPIDEMIOLOGA

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

En una encuesta a nivel nacional holands en 2003, la prevalencia fue al menos el 0,002% de los nacimientos (4 casos por cada 189.000 RN) para los aos 1996-1998

En 2007, la Fundacin Sndrome de Moebius es.m que 2.000 personas de todo el mundo .enen la condicin

SNDROME DE MOEBIUS

Neurology. Aug 12 2003;61(3):327-33.

Am J Matern Child Nurs. Sept/Oct, 2008;33(5):272-278.

CLASIFICACIN

En 1979, Towfighi et al propuso un sistema de clasificacin en base a diferencias patolgicas observadas en estudios de pacientes con el sndrome

SNDROME DE MOEBIUS

Acta Neuropathol (Berl). Oct 1979;48(1):11-7.

SIN CORRELACIN CLNICA SIGNIFICATIVA

Grupo I Hipoplasia simple o atrofia de los ncleos PC

Grupo II Lesiones primarias a nivel perifrico de los PC

Grupo III Necrosis focal, gliosos y calcificacin en ncleos PC

Grupo IV Miopaqa primaria sin lesiones en PC o SNC

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 VI al XII, con preservacin general del VIII VII en todos los casos VI 75% XII minora

PC III y IV en raras ocasiones

SNDROME DE MOEBIUS

PATOGENIA

MLTIPLES TEORAS: Moebius crea que la condicin era de origen degeneraHva o txica y que involucraba a los ncleos de los nervios afectados

Algunos autores sugieren que se debe a una hipoplasia o agenesia congnita hereditaria de los ncleos PC

Displasia mesodrmica que involucra la musculatura derivada de los 1er y 2 arcos branquiales Esta teora sos.ene que los cambios del tronco cerebral son secundarios a la atrofia retrgrada de los PC

SNDROME DE MOEBIUS

PATOGENIA

Malformaciones de las extremidades asociadas a la disfuncin de los PC sugieren una interrupcin de la morfognesis normal, con mayor probabilidad en las semanas 4-7 de gestacin

SNDROME DE MOEBIUS

ETIOLOGA

Controversial MulHfactorial Por definicin, las lesiones traum.cas no son parte del sndrome

SNDROME DE MOEBIUS

Gen.ca Dao

hipxico/isqumico

Exposicin prenatal a txicos

Aprox. 2% Mayora espordicos

Neurology. Aug 12 2003;61(3):327-33.

ETIOLOGA: TEORA VASCULAR

1. Interrupcin del flujo a nivel de la arteria basilar o regresin prematura de las arterias trigeminales primi.vas

2. Interrupcin del flujo de la arteria subclavia que implica la interrupcin del flujo de sangre embrionario

SNDROME DE MOEBIUS

BMJ Case Reports 2011; doi:10.1136/bcr.09.2010.3331 1 of 3

BACKGROUND Moebius syndrome 1 3 has not previously been described in an infant born to a mother with homocystinuria, and this association may lend weight to the theory of an early vas-cular insuffi ciency or disruption in the fetus as one of the possible aetiologies. In addition, the literature would sug-gest that most pregnancies to mothers with homocystinu-ria do not result in an abnormal baby and the greatest risk of the pregnancy is to the mothers health due to her heightened hypercoaguability; however this case report suggest that congenital abnormality in infant is possible.

CASE PRESENTATION A female infant, birth weight 2755 g, was born at term by a normal vaginal delivery to a mother known to have pyri-doxine-unresponsive homocystinuria. The pregnancy was unplanned and the mother complied poorly with her med-ications and diet. She had learning diffi culties and suffered from depression. She was known to have high methionine levels. She had a history of a left subclavian thrombosis. She was on warfarin at conception which was changed to low molecular weight heparin during the pregnancy. She was also treated with betaine and folic acid. She suffered from asthma and was on fl ixotide, seretide and salbuta-mol. Antenatal scans demonstrated bilateral talipes, a ven-triculoseptal defect and a possible coarctation of the aorta. An underlying syndrome was suspected. The mother was tested for myotonic dystrophy, which was negative. The mother had a long labour and was on an infusion of fenta-nyl. At delivery, the baby required resuscitation, thought at the time to be due to the maternal analgesia. Apgar scores were 2 at 1 min, 6 at 5 min and 9 at 10 min. She was intubated and ventilated initially and then required non-invasive respiratory support for 5 days. After delivery, she was noted to have a paucity of facial expression and uncoordinated swallowing in addition to the antenatally noted bilateral talipes. A diagnosis of Moebius syndrome was suspected clinically.

INVESTIGATIONS A postnatal echocardiogram confi rmed the presence of a VSD but excluded a coarctation. Genetic evaluation sup-ported a diagnosis of Moebius syndrome. Chromosomes showed a normal 46 XX karyotype. The infant was nega-tive for homocystinuria. An MRI of her brain showed a normal brain structure with a small volume right posterior fossa. Her hearing was normal.

OUTCOME AND FOLLOW-UP A multidisciplinary team of speech and language thera-pists, neurologists, geneticists and orthopaedic surgeons was put in place for her ongoing management. She had severe gastro-oesophageal refl ux and required nasojejunal feeding. At 5 months of age she had a laparoscopic Nissen fundoplication and percutaneous endoscopic gastrostomy insertion.

DISCUSSION The complete pathophysiology of Moebius remains unclear. The cranial nerves which may be involved include VIXII, usually with sparing of VIII. Cranial nerves III and IV can also be involved but rarely. Cranial nerve VII is always involved, and VI, the abducens nerve, is involved in 75% of cases. In Moebiuss original description of the condition, he considered there to be a degenerative or toxic process involving the nuclei of the affected nerves. 4 5 It is quite likely that more than one aetiology can cause the features of Moebius syndrome. Approximately 2% of cases appear to have a genetic basis. 6 Towfi ghi postulated four aetiological groups 7 from neuropathological studies on 15 cases. Group I was characterised by hypoplasia of the cranial nerve nuclei from a primary congenital rhom-bomeric maldevelopment (sometimes referred to as the antegrade theory). Group II was characterised by neuronal loss and degeneration secondary to a defect in peripheral facial nerve (the retrograde theory). Group III was char-acterised by decreased neurons with degeneration, focal

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]

Summary A case of Moebius syndrome is reported in an infant of a mother known to have pyridoxine-unresponsive homocystinuria. The authors suggest that Moebius syndrome could result from early vascular insuffi ciency or disruption occurring early in development related to maternal homocystinuria.

Moebius syndrome consists of congenital complete or partial facial nerve palsy with or without paralysis of other cranial nerves and often in association with other malformations of the limbs and orofacial structures, but usually without gross structural brain abnormalities.

BMJ Case Reports 2011; doi:10.1136/bcr.09.2010.3331

ETIOLOGA: GENTICA

Sndrome listado en OMIM con gen locus 13q12.2-q13 Uzumcu et al. no encontr microdeleciones en esta regin crHca en 9 pacientes y excluy varios genes candidatos (FGF9, GSH1 y CDX2)

Ambos informes sugieren que un gen responsable se encuentra en la regin 13q12.2-q13

SNDROME DE MOEBIUS

-Online Mendelian Inheritance in Man. %157900 - MOEBIUS SYNDROME; MBS. OMIM - Online Mendelian Inheritance in Man.

Eur J Med Genet. Sep-Oct 2009;52(5):315-20.

1977 Variante de SM con una translocacin recproca t(1p34; 13q13), en al menos 7 miembros de una familia afectada de ms de 3 generaciones

1991 Nia de 2 aos con SM con una delecin de la banda q12.2 del cr 13 Cario.po de la madre normal

Ziter FA, et al. Arch Neurol. Jul 1977;34(7):437-42.

Slee JJ, et al. J Med Genet. Jun 1991;28(6):413-4.

ETIOLOGA: GENTICA

Tambin se han reportado casos familiares

SNDROME DE MOEBIUS

1996 Gran rbol genealgico con SM AD consistente en gran parte de paresia facial bilateral asimtrica

Despus de la exclusin de la regin 13q12.2-13, localizaron un gen en 3q21-22

1997 Nio con sd. Mbius-like (dipleja facial y ptosis pero con mov. extraoculares normales y sin anomalas esquel.cas) con una translocacin recproca entre los cromosomas 1 y 2 (p22.3, q21.1)

Kremer H, et al. Hum Mol Genet. Sep 1996;5(9):1367-71.

Nishikawa M, et al. Clin Genet. 1997;51(2):122-3.

GENTICA? HERENCIA?

Debido a la inconsistencia en la definicin de la patologa, el rol de la herencia en el sndrome de Moebius sigue siendo poco claro

Se han descrito genealogas con herencia AD, AR, y ligada al X recesiva

SNDROME DE MOEBIUS

ETIOLOGA: TXICOS

Estudio de nios en Brasil de 1998 Fuerte asociacin entre SM y uso prenatal de misoprostol

Se cree que causa un evento isqumico en el tronco cerebral embrionario temprano en la gestacin

102 C. Vauzelle et al. / Reproductive Toxicology 36 (2013) 98 103

Table 5Published studies on misoprostol malformative risk.

AuthorLocation

MethodologyReason for misoprostol use

Number of women or infantsuse of other abortifacients

Results

Schler et al. [15],Brazil

Prospective studyMostly self-attemptedabortions (95%)

86 misoprostol-exposed pregnanciesvs. 86 pregnancies exposed tonon-teratogens

Major birth defects among life births:2/67 vs. 2/81RR = 1.21 (95% CI = 0.178.35)Birth defects in the misoprostol group:- constriction rings of the arms- hepatosplenomegaly, pulmonaryhypertension, persistent fetalcirculation

31.4% in the exposed group usedanother abortifacient

Dal Pizzol Tda et al. [16],Brazil

Prospective cohort:Brazilian Study onGestational Diabetes.Misoprostol used toinduce menstruation

120 misoprostol exposed pregnanciesvs. 4575 pregnancies without exposureto misoprostol

Birth defects: 5/118 vs. 81/4575Adjusted OR = 2.64 (95% CI = 1.036.75)Birth defects in the misoprostol group:- myelomeningocele- clubfoot- syndactyly- fingernail defect- microcephaly

No information on other abortifacients No information on time of exposure

Barbero et al. [17],Argentina

Prospective studyMostly self-attemptedabortions (81%)

94 misoprostol-exposed pregnanciesvs. 401 pregnancies exposed tonon-teratogens

Major birth defects among life births:5/77 vs. 8/372Adjusted RR = 3.80 (95%CI = 1.0514.61)Birth defects in the misoprostol group:- encephalocele, transverse limbdefects, constriction ring- porencephaly- pulmonary adenomatous cysticmalformation- occipital encephalocele- intestinal malrotation

35.2% in the exposed group usedanother abortifacient

Pastuszak et al. [11],Brazil

Case-control studyMostly self-attempted abortions(98%)

96 infants with Moebiussyndrome vs.96 infants with neural-tube defects

Misoprostol exposure amongMoebiussyndrome vs. neural tubedefects:OR = 29.7 (95% CI = 11.676.0)

Brasil et al. [14],Brazil

Case-control study nested in acohort of very low birth weightinfants.Self-attempted abortions

37 infants with birth defects vs. 387controls without birth defects

Misoprostol exposure among birthdefects vs. controls:6/37 vs. 28/387OR = 2.4 (95% CI = 1.06.2)

Orioli and Castilla [10],Brazil

Case-control studySelf-attempted abortions

4673 infants with birth defects vs.4980 non-malformed infants

Misoprostol exposure among birthdefects vs. controls:- All birth defects 34/4673 vs. 23/4980!2 = 2.42 p > 0.05- Terminal transverse limb reductionOR = 12.04 (95% CI = 3.5241.12)- Constriction rings or skin scarsOR = 40.72 (95% CI = 10.83153.12)- Arthrogryposis OR = 8.47 (95%CI = 1.9536.74)- Hydrocephalus OR = 4.23 (95%CI = 1.4715.15)- Equinovarus feet OR = 1.02 (95%CI = 0.244.28)

Vargas et al. [12],Brazil


93 infants with vascular disruption vs.279 malformed infants with otherkinds of congenital anomalies

Misoprostol exposure among cases vs.controls:- All vascular disruptive birth defectsOR = 22.0 (95% CI = 7.381.3)- Moebius OR = 49.0 (95%CI = 7.071907)- Terminal transverse limb reductionOR = 24.0 (95% CI = 3.0099.1)- Other vascular disruption anomaliesas a group OR = 7.5 (95% CI = 1.2378.7)

Opaleye et al. [13],Brazil


126 malformed infants vs. 126 controlswithout birth defects

Misoprostol exposure among cases vs.controls:7/119 vs. 2/124 OR = 3.65 (95%CI = 0.7417.91)3 out of the 7 malformed infants wereexposed during the second trimester.

Volume 338 Number 26

1881

USE OF MISOPROSTOL DURING PREGNANCY AND MBIUS SYNDROME IN INFANTS

USE OF MISOPROSTOL DURING PREGNANCY AND MBIUS SYNDROME IN INFANTS

A

NNE

L. P

ASTUSZAK

, M.S

C

., L

AVINIA

S

CHLER

, M.D., P

H

.D., C

ARLOS

E. S

PECK

-M

ARTINS

, M.D., K

ATIA

-E

DNI

F.A. C

OELHO

, M.D., S

YNTHIA

M. C

ORDELLO

, M.D., F

ERNANDO

V

ARGAS

, M.D., D

ECIO

B

RUNONI

, M.D., P

H

.D., I

DA

V.D. S

CHWARZ

, M.D., M

ARIELA

L

ARRANDABURU

, M.D., H

ELOISA

S

AFATTLE

, M.D., V

ERA

F.A. M

ELONI

, M.D.,

AND

G

IDEON

K

OREN

, M.D.

A

BSTRACT

Background

Patients with upper gastrointestinalulceration may be treated with misoprostol, but it isnot recommended for pregnant women because itmay stimulate uterine contractions and cause vagi-nal bleeding and miscarriage. Recent data from Bra-zil, where misoprostol is used orally and vaginally asan abortifacient, have suggested a relation betweenthe use of misoprostol by women in an unsuccessfulattempt to terminate pregnancy and Mbius syn-drome (congenital facial paralysis) in their infants.

Methods

We compared the frequency of miso-prostol use during the first trimester by mothers ofinfants in whom Mbius syndrome was diagnosedand mothers of infants with neural-tube defects inBrazil. All diagnoses in infants were made betweenJanuary 16, 1990, and May 31, 1996, by clinical genet-icists at seven hospitals who also interviewed themothers and recorded information about the admin-istration of misoprostol, among other data.

Results

We identified 96 infants with Mbiussyndrome and matched them with 96 infants withneural-tube defects. The mean age at the time of thediagnosis of Mbius syndrome was 16 months(range, 0.5 to 78), and the diagnosis of neural-tubedefects was made within 1 week of birth in mostcases. Among the mothers of the 96 infants withMbius syndrome, 47 (49 percent) had used miso-prostol in the first trimester of pregnancy, as com-pared with 3 (3 percent) of the mothers of the 96 in-fants with neural-tube defects (odds ratio, 29.7; 95percent confidence interval, 11.6 to 76.0). Twenty ofthe mothers of the infants with Mbius syndromehad taken misoprostol only orally (odds ratio, 38.8;95 percent confidence interval, 9.5 to 159.4), 20 hadtaken misoprostol both orally and vaginally, 3 hadtaken the drug vaginally, and 4 did not report howthey took the drug.

Conclusions

Attempted abortion with misopros-tol is associated with an increased risk of Mbiussyndrome in infants. (N Engl J Med 1998;338:1881-5.)

1998, Massachusetts Medical Society.

From the Motherisk Program, Hospital for Sick Children, and the FetalDiagnosis and Treatment Centre, University of Toronto, Toronto (A.L.P.,G.K.); Departmento de Genetica, Universidade Federal do Rio Grande doSul, Porto Alegre, Brazil (L.S.); Unidade de Genetica, Hospital de Clinicasde Porto Alegre, Brazil (L.S., I.V.D.S., M.L.); Setor de Genetica, Rede deHospitais Sarah, Brasilia, Brazil (C.E.S.-M., H.S.); Setor de Genetica, Redede Hospitais Sarah, Salvador, Brazil (K.-E.F.A.C., S.M.C.); Setor de Genet-ica, Hospital Universitario Gaffre-Guinle, Rio de Janeiro, Brazil (F.V.); andDisciplina de Genetica, Escola Paulista de Medicina, Universidade Federalde So Paulo, and Unidade de Citogenetica, Hospital dos Servidores Pub-licos do Estado de So Paulo, So Paulo, Brazil (D.B., V.F.A.M.). Addressreprint requests to Dr. Pastuszak at the Fetal Diagnosis and TreatmentCentre, University of Toronto, Hospital for Sick Children, 555 UniversityAve., Toronto, ON M5G 1X8, Canada.

Jordo C. Neto, M.D. (Disciplina de Genetica, Escola Paulista de Me-dicina, Universidade Federal de So Paulo, and Unidade de Citogenetica,Hospital dos Servidores Publicos do Estado de So Paulo, So Paulo, Bra-zil) was also an author.

ISOPROSTOL is a synthetic prosta-glandin E

1

analogue with greater anti-secretory and mucosal-protective ac-tivity than natural prostaglandins. It is

used to prevent and treat gastrointestinal lesions in-duced by nonsteroidal antiinflammatory drugs andupper gastrointestinal ulceration. It is not recom-

M

mended for use during pregnancy, because it maystimulate uterine contractions and cause vaginalbleeding, which may endanger fetal survival. Thecombination of misoprostol and mifepristone ormethotrexate has been used for the elective induc-tion of abortion.

1,2

In Brazil, where elective abor-tions are prohibited, 57 to 75 percent of womenwho attempt abortion use misoprostol, which canbe obtained over the counter.

3-5

However, misopros-tol often fails to induce abortion during the first tri-mester,

6

and up to 80 percent of the pregnancies inwomen who use this agent continue to term.

Although misoprostol has no teratogenic actionsin pregnant rats

7-9

and mice,

10

there are reports ofMbius syndrome (congenital facial paralysis, withor without limb defects) in infants whose motherstook misoprostol in an unsuccessful attempt at abor-tion.

11-14

In one study, in a small cohort of 20 womenwho used misoprostol unsuccessfully as an abortifa-cient during the first trimester, 3 had a second-tri-mester abortion, and 17 gave birth to infants withoutmalformations.

15

The purpose of our study was tocompare the frequency of misoprostol use during thefirst trimester of pregnancy between mothers of in-fants with Mbius syndrome and mothers of infantswith neural-tube defects.

METHODS

Subjects

Between January 16, 1990, and May 31, 1996, 96 infants 0.5to 78 months of age were given a diagnosis of Mbius syndromeby geneticists at seven hospitals in Brazil. Mbius syndrome wasdefined as bilateral or unilateral facial-nerve paralysis (paralysis of

The New England Journal of Medicine Downloaded from nejm.org by DANIELA CASTILLO VILLAGRAN on May 15, 2014. For personal use only. No other uses without permission.

Copyright 1998 Massachusetts Medical Society. All rights reserved.

N Engl J Med. 1998 Jun 25;338(26):1881-5.

SNDROME DE MOEBIUS

65

Rev. Med. FCM-UCSG, Ao 2011, vol.17 N1. PGS. 65-69ISSN - 1390-0218

Clinical case report: Moebius syndrome associated with the use of misoprostol in pregnancy

Mara Fernanda Caldern Len1, Lennys Viviana Calle Morillo1, Javier Aquiles Hidalgo Acosta2

1 Universidad Catlica de Santiago de Guayaquil, Facultad de Ciencias Mdicas, Guayaquil, Ecuador2Hospital IESS, Portoviejo, Ecuador

RESUMEN

El sndrome de Moebius conocido tambin como diplejia facial congnita o agenesia nuclear, es una enfermedad neurolgica cong-nita poco frecuente en la que se ven afectados los ncleos de origen de los pares craneales VI y VII, impidiendo su total desarrollo.

describe el caso clnico de un paciente de 11 meses de edad cuya madre us tabletas de misoprostol por va vaginal (400 mcg),

no siendo as en el primer trimestre de gestacin, donde los efectos son devastadores provocando un aborto, o en su defecto,

legal, el misoprostol se emplea para la interrupcin del embarazo, sin embargo la infrecuente supervisin profesional, llevan a

de anomalas congnitas. El presente trabajo demuestra la injerencia del misoprostol como agente teratgeno durante el primer trimestre de embarazo y posible inductor al desarrollo del sndrome de Moebius.Palabras clave

ABSTRACT

The Moebius syndrome, also known as congenital facial diplegia or nuclear agenesis, is a rare congenital neurological disorder

associated with the use of teratogenic substances such as cocaine, thalidomide, misoprostol, etc. The clinical case of an 11-month

possible inducer of the development of the Moebius syndrome. Key words

Correspondencia a:

Dra. Viviana Calle Morillo

Correo electrnico: [email protected]

Recibido: 29 de abril de 2011

Aceptado: 15 de diciembre de 2011

Reporte de caso clnico: sndrome de Moebius asociado al uso de misoprostol en el embarazo

67Rev. Med. FCM-UCSG, Ao 2011, vol.17 N1

SD DE MOEBIUS ASOCIADO AL USO DE MISOPROSTOL

-

Exmenes complementarios

izquierda.

cortical. Cariotipo: normal sin aneoploidias, lo que descar-

y velocidad de conduccin de nervios faciales: es--

al momento del estudio severo aunque sin activi-dad denervatoria.

Discusin

La etiologa del SM es generalmente idioptica, -

relaciona con eventos que puedan producir una -

turas irrigadas por la arteria subclavia primitiva.8,9

asociar este frmaco con la ocurrencia de anoma-las congnitas provienen de informes de casos y de estudios epidemiolgicos de casos y controles.

de abortos en embarazadas expuestas al misopros-tol, aunque con la misma proporcin de nios na-cidos con malformaciones.

Figura 1. comisura labial desviada hacia el lado

Figura 2. se observa lagoftalmia en ojo derecho

Figura 3. Canto externo con desviacin antimongoloide

Figura 4. Se observa estado hipotnico del nio y facie inexpresiva.

502 CARTA AL EDITOR

G. Salazara,, D. Cuelloa, M. Fragosoa y L. Benllocb

a Servei de Neurologia, Hospital Consorci Sanitari deTerrassa, Barcelona, Espanab Servei de Psiquiatra, Hospital Consorci Sanitari deTerrassa, Barcelona, Espana

Autor correspondencia.Correo electrnico: [email protected] (G. Salazar)

doi:10.1016/j.nrl.2011.01.020

Primer caso de sndrome deMoebius-Poland en nino expuestoprenatalmente a misoprostol

First case of Moebius-Poland syndrome in childprenatally exposed to misoprostol

Sr. Editor:

El sndrome de Moebius (OMIM 157900) se caracteriza porparlisis facial con alteracin de la abduccin ocular. El ner-vio facial (VII nervio craneal) y nervio abducens (VI nerviocraneal) son ms frecuentemente involucrados, pero otrosnervios craneales pueden estar involucrados tambin. Elfenotipo es variable y puede incluir defectos congnitos oro-faciales y de las extremidades1.

La secuencia de Poland (OMIM 173800) se caracteriza porla presencia de braquisindactilia unilateral y aplasia ipso-lateral de la porcin esternocostal del msculo pectoralmayor. Algunas veces se denomina sndrome de Poland porser inicialmente descrito por Poland2.

La combinacin del sndrome de Moebius y Polandse presenta raramente y se ha estimado una prevalen-cia de 1 en 500.000; en la literatura revisada no seencontr esta asociacin en expuestos prenatalmente amisoprostol3.

Se presenta un reporte de sndrome de Moebius y Polanden un neonato expuesto prenatalmente a misoprostol.

Paciente hijo de madre de 18 anos, quien consult pordismorfismo facial, encontrndose al examen fsico parlisisfacial bilateral, cara redondeada, fisuras palpebrales delga-das, labios en arco de cupido, paladar ojival, micrognatia,hipoplasia de pectoral mayor con ausencia de tetilla (ate-lia), adems se encuentra sindactilia proximal del segundoy tercer dedo, y pie equinovaro bilateral (figs. 1 y 2). Comoantecedente de importancia se encuentra que la madre uti-lizo por va oral y vaginal a las 5 semanas de gestacin 400 !gde misoprostol con fines abortivos, presentando sangradoescaso.

El misoprostol es un anlogo sinttico de la prosta-glandina E1 aprobado segn las entidades reguladoras demedicamentos de muchos pases para la prevencin y eltratamiento de lceras gstricas asociadas con el uso deantiinflamatorios no esteroideos, por su efecto antisecretorde cidos gstricos. La exposicin prenatal a misoprostolse ha asociado a la ocurrencia de defectos por disrupcinvascular, principalmente la secuencia de Moebius y defectosde las extremidades de tipo terminal y transversal4,5.

Las anormalidades en la estructura vascular pueden sersecundarias a efectos teratgenos. Los teratgenos puedenactuar directamente disminuyendo el flujo sanguneo o en

el desarrollo de los vasos sanguneos cambiando la anatomay/o la estructura6,7. Las anormalidades vasculares de laarteria subclavia derecha observada en sndrome de Polandpueden relacionarse con una disrupcin vascular causada pormisoprostol durante un perodo crtico5,8.

Figura 1 Ntese fenotipo tpico de sndrome de Moebius-Poland, hipoplasia del pectoral con atelia y pie equinovaro.

Figura 2 Ntese la parlisis facial bilateral, caractersticatpica del sndrome de Moebius.

Documento descargado de http://zl.elsevier.es el 14/05/2014. Copia para uso personal, se prohbe la transmisin de este documento por cualquier medio o formato.

502 CARTA AL EDITOR

G. Salazara,, D. Cuelloa, M. Fragosoa y L. Benllocb

a Servei de Neurologia, Hospital Consorci Sanitari deTerrassa, Barcelona, Espanab Servei de Psiquiatra, Hospital Consorci Sanitari deTerrassa, Barcelona, Espana

Autor correspondencia.Correo electrnico: [email protected] (G. Salazar)

doi:10.1016/j.nrl.2011.01.020

Primer caso de sndrome deMoebius-Poland en nino expuestoprenatalmente a misoprostol

First case of Moebius-Poland syndrome in childprenatally exposed to misoprostol

Sr. Editor:

El sndrome de Moebius (OMIM 157900) se caracteriza porparlisis facial con alteracin de la abduccin ocular. El ner-vio facial (VII nervio craneal) y nervio abducens (VI nerviocraneal) son ms frecuentemente involucrados, pero otrosnervios craneales pueden estar involucrados tambin. Elfenotipo es variable y puede incluir defectos congnitos oro-faciales y de las extremidades1.

La secuencia de Poland (OMIM 173800) se caracteriza porla presencia de braquisindactilia unilateral y aplasia ipso-lateral de la porcin esternocostal del msculo pectoralmayor. Algunas veces se denomina sndrome de Poland porser inicialmente descrito por Poland2.

La combinacin del sndrome de Moebius y Polandse presenta raramente y se ha estimado una prevalen-cia de 1 en 500.000; en la literatura revisada no seencontr esta asociacin en expuestos prenatalmente amisoprostol3.

Se presenta un reporte de sndrome de Moebius y Polanden un neonato expuesto prenatalmente a misoprostol.

Paciente hijo de madre de 18 anos, quien consult pordismorfismo facial, encontrndose al examen fsico parlisisfacial bilateral, cara redondeada, fisuras palpebrales delga-das, labios en arco de cupido, paladar ojival, micrognatia,hipoplasia de pectoral mayor con ausencia de tetilla (ate-lia), adems se encuentra sindactilia proximal del segundoy tercer dedo, y pie equinovaro bilateral (figs. 1 y 2). Comoantecedente de importancia se encuentra que la madre uti-lizo por va oral y vaginal a las 5 semanas de gestacin 400 !gde misoprostol con fines abortivos, presentando sangradoescaso.

El misoprostol es un anlogo sinttico de la prosta-glandina E1 aprobado segn las entidades reguladoras demedicamentos de muchos pases para la prevencin y eltratamiento de lceras gstricas asociadas con el uso deantiinflamatorios no esteroideos, por su efecto antisecretorde cidos gstricos. La exposicin prenatal a misoprostolse ha asociado a la ocurrencia de defectos por disrupcinvascular, principalmente la secuencia de Moebius y defectosde las extremidades de tipo terminal y transversal4,5.

Las anormalidades en la estructura vascular pueden sersecundarias a efectos teratgenos. Los teratgenos puedenactuar directamente disminuyendo el flujo sanguneo o en

el desarrollo de los vasos sanguneos cambiando la anatomay/o la estructura6,7. Las anormalidades vasculares de laarteria subclavia derecha observada en sndrome de Polandpueden relacionarse con una disrupcin vascular causada pormisoprostol durante un perodo crtico5,8.

Figura 1 Ntese fenotipo tpico de sndrome de Moebius-Poland, hipoplasia del pectoral con atelia y pie equinovaro.

Figura 2 Ntese la parlisis facial bilateral, caractersticatpica del sndrome de Moebius.

Documento descargado de http://zl.elsevier.es el 14/05/2014. Copia para uso personal, se prohbe la transmisin de este documento por cualquier medio o formato.

doi:10.1016/j.nrl.2011.01.019

SNDROME DE MOEBIUS

ETIOLOGA: TXICOS

Otros txicos descritos asociados: Ergotamina Cocana Frmaco: Zonisamida

SNDROME DE MOEBIUS

-Smets K, at al. Ergotamine as a possible cause of Mbius sequence: addi.onal clinical observa.on. J Child Neurol. May 2004;19(5):398. -Puvabanditsin S, et al. Poland-Mbius 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.

CUADRO CLNICO

Jos Gabriel Lora F., Jean Pierre Certain Y.Acta de Otorrinolaringologa &

Ciruga de Cabeza y Cuello

DISCUSIN

El sndrome de Mobius es un desorden neurolgicocaracterizado por parlisis de los nervios craneales,usualmente involucrando el nervio facial y el nervio motorocular externo (3). La parlisis usualmente es bilateral y otrosnervios craneales pueden verse involucrados. Diferentesmalformaciones craneofaciales, musculoesquelticas,cardiacas y el retardo mental pueden asociarse dando origenal sndrome Mobius-like (3).

El caso en este reporte es similar a otros casos reportadosanteriormente debido a que estn afectados el nervio facial,el nervio motor ocular externo y presenta una alteracinmusculoesqueltica que la escoliosis toraco-lumbar quepresenta. Las caractersticas inusuales de este paciente sonque la afectacin es unilateral y que adems el pacientepresenta compromiso auditivo severo. Un dficit auditivoneural slo se observa en aproximadamente el 10% de loscasos de sndrome de mobius y usualmente indica unaalteracin a nivel del conducto auditivo interno (13, 14).Este paciente en particular pertenece a ese 10% de pacientescon alteracin en el VIII par y como el TAC lo demuestra laalteracin evidente se encuentra a nivel de conducto auditivointerno, en este caso especficamente lo observado es unaestenosis severa del conducto auditivo interno, lo cual escompatible con una aplasia o hipoplasia del nerviovestibulococlear.

La etiologa exacta de este sndrome se desconoce.Diferentes esquemas etiolgicos se han planteado paracomprender la patognesis de esta entidad. stos se resumende la siguiente manera: 1) aplasia o hipoplasia de los ncleosde nervios craneales 2) destruccin nuclear 3) anormalidadesperifricas y 4) miopatas primarias (15). Se ha planteadodada su gran variabilidad de presentacin que esta entidad ysus variantes resultan de un evento hipxico-isqumico. Sepropone una interrupcin del flujo sanguneo por compresinde los vasos fetales cerca del origen de los ncleos cranealeso una alteracin en el desarrollo de la vasculatura cerebral(6, 7). Una etiologa gentica tambin se ha planteado y sebasa en hallazgos en ciertas familias con sndrome de Mobiuscon herencia autosmica dominante (6).

Estudios neuropatolgicos demuestran atrofia o necrosisa nivel del tallo cerebral (15). Estos hallazgos asociados aalteraciones imagenolgicas tambin a nivel del tallocerebral identificadas mediante resonancia magntica (16,17) y estudios electrofisiolgicos realizados en pacientescon sndrome de Mobius (18) sugieren que esta entidad esun desorden complejo del desarrollo del tallo cerebral, msque la ausencia de ciertos ncleos de nervios craneales (5).

Figuras 3. Limitacin para la abduccin del globo ocular izquierdo.

Figura 1. Paresia de la musculatura frontal izquierda

Figuras 2. Sonrisa asimtrica, por la paresia facial

Parlisis Facial Espectro au.sta

Discapacidad Intelectual Hipogonadismo?

SNDROME DE MOEBIUS

PARLISIS FACIAL

La dipleja facial es el sntoma ms notable Puede ser observado poco despus del nacimiento Cierre incompleto del prpado durante el sueo Babeo y dificultad para la succin

Incapacidad para cerrar los labios, prominencia del labio superior En adultos Labio inferior generalmente ever.do y prominente

SNDROME DE MOEBIUS

TRASTORNOS DEL HABLA 76-90%

Briegel W. Neuropsychiatric findings of Mobius sequence -- a review. Clin Genet. Aug 2006;70(2):91-7.

Comp. funcional de labios, lengua, paladar, laringe Malformaciones orofaciales: paladar hendido, microgna.a y microglosia DI o prdida de la audicin Disartria flcida

ESPECTRO AUTISTA

En 1989, Gillberg y Steffenburg Sntomas auHstas presentes en el 30-40% de nios y adultos jvenes con SM

Confirmado en otras series:

SNDROME DE MOEBIUS

Acta Paediatr Scand. Mar 1989;78(2):314-6

be extensively reduced or even impossible due tocranial nerve palsies. Other diagnostic difficultiesresult from developmental delays, especiallyspeech and language delays, and most of all a concomitant mental retardation. Therefore, theyounger the patient, the more difficult a diagnosisof autistic disorder.Additionally, there are methodological prob-

lems of the studies mentioned above: questionablerepresentativeness (all studies), lack of informa-tion about instruments used (2), and antiquatedmethods (47). Furthermore, nearly all patientsdiagnosed with autism were mentally retarded(12, 47, 48), and mental retardation was over-represented in at least two studies (12, 47). To sumit up, there is only one association that could beundoubtedly shown in most of the studies onMobius sequence (12, 47, 48): the association ofautism with mental retardation, which is alreadywell known (69). Representative studies on largerpopulations are needed to show if there is really anassociation of Mobius sequence with autism.Until now, there have been neither systematic

studies nor case reports on other psychiatric dis-orders in Mobius patients.

Conclusions

There are a lot of unanswered questions that arerelevant for counselling and treating patientswith Mobius sequence. With regard to neuropsy-chiatric aspects, studies on intellectual capacities,academic achievement, behaviour, and psychiat-ric disorders using standardized instruments fordifferent age groups are needed. Because of thelow prevalence of the sequence, multicentre orinternational studies could be helpful to recruitenough patients.As Mobius sequence can be associated with

a variety of anomalies, multidisciplinarity in diag-nosis and treatment is necessary. Recognizing,encouraging, and reinforcing strengths and resil-iencies (50) are at least as important as sufficient

and in-time treatment of deficits. For many pa-tients, contact to and support by the Mobiusfoundation could be very helpful.

Acknowledgement

The author is grateful to Moebius Syndrom Deutschland e.V.,the German Mobius association, for providing him with thephotograph. He also thanks O. Steinlein, Munich, for her helpwith the chapter on aetiology.

References

1. Kuklik M. Poland-Mobius syndrome and disruptionspectrum affecting the face and extremities: a review paperand presentation of five cases. Acta Chir Plast 2000: 42: 95103.

2. Verzijl HTFM, van der Zwaag B, Cruysberg JRM et al.Mobius syndrome redefined. A syndrome of rhombence-phalic maldevelopment. Neurology 2003: 61: 327333.

3. Gorlin RJ, Cohen MM Jr, Levin LS. Syndromes of thehead and neck. Oxf Monogr Med Genet 1990: 19: 666674.

4. Kumar D. Moebius syndrome. J Med Genet 1990: 27: 122126.

5. von Graefe A. In: von Graefe A, Saemisch T, eds.Handbuch der gesammten Augenheilkunde, Vol. 6. Leip-zig, Germany: Engelmann, 1880: 148.

6. Mobius PJ. Uber angeborene doppelseitige Abducens-Facialis-Lahmung. Munch Med Wochenschr 1888: 35: 9194.

7. Henderson JL. The congenital facial diplegia syndrome:clinical features, pathology, and aetiology. A review ofsixty-one cases. Brain 1939: 62: 381403.

8. Sudarshan A, Goldie WD. The spectrum of congenitalfacial diplegia (Moebius syndrome). Pediatr Neurol 1985: 1:180184.

9. MacDermot KD, Winter RM, Taylor D et al. Oculofacialpalsy in mother and son: review of 26 reports of familialtransmission within the Mobius spectrum of defects.J Med Genet 1990: 27: 1826.

10. Richards RN. The Moebius syndrome. J Bone Joint Surg1953: 35A: 437444.

11. Creak EM. Childhood psychosis. Br J Psychiatry 1963: 109:8489.

12. Bandim JM, Ventura LO, Miller MT et al. Autism andMobius sequence. An exploratory study of children innortheastern Brazil. Arq Neuropsiquiatr 2003: 61: 181185.

13. Cronemberger MF, de Castro Moreira JB, Brunoni D et al.Ocular and clinical manifestations of Mobius syndrome.J Pediatr Ophthalmol Strabismus 2001: 38: 156162.

Table 1. The occurrence of autistic disorders in recent studies on Mobius sequence

StudiesAutisticpatients

Mental retardationamong autisticpatients (%)

Patientsage (years)

Autism-specificinstruments

Classificationsystems

Gillberg andSteffenburg (47)

5/17 80 234 Check-list for autism (11) DSM-III-R

Johansson et al. (48) 6/22 100 122 ABC, CARS, ADI-R DSM-III-R, ICD-10Bandim et al. (12) 5/23 100 111 CARS DSM-IVVerzijl et al. (2) 2/37 No information 0.553 No information No information

ABC, Autism Behaviour Check-List (66); ADI-R, Autism Diagnostic Interview Revised (68); CARS, Childhood Autism-RatingScale (67).

Neuropsychiatry of Mobius sequence

95


Table 1ASCs and neurodevelopmental background factors in Mobius CHARGE and OAV groups.

Mobius CHARGE OAV

n=25 (Male:female) n=31 (Male:female) n=20 (Male:female)

Total group n=25 (18:7) n=31 (15:16) n=20 (12:8)Diagnosed re ASC n=21a (16:5) n=25b (11:14) n=19c (11:8)

Total groupAge range, yrs 1 month55 1 month31 8 months17Mean age (S.D.), yrs 12:4 (11:7) 8:11 (6:7) 8:1 (5:3)CI, yrs 7:6-17:1 6:6-11:4 5:5-10:4

DiagnosedAge range, yrs 1:1155 2:431 1:1117Mean age (S.D.), yrs 13:11 (11:5) 9:1 (4:11) 8:3 (5:1)CI, yrs 8:1019:0 7:111:2 5:1010:8

ASCd,e 10 17 8AD 6 (MMR 2, SMR 4) 5 (MMR 1, PMR 4) 2 (MMR 1, SMR 1)ALC 1 (MMR) 5 (NA 1, MMR 1, SMR 1, PMR 2) 1 (A)AT 3 (NA 3) 7 (MMR 5, SMR 2) 5 (NA 1, MMR 1, SMR 2, PMR 1)AT? 3 (A 2, NA 1) 3 (MMR 1, NA 2) 3 (NA 1, MMR 2)No suspicion of ASCs 8 (A 6, NA 2) 5 (A 1, NA 2, MMR 2) 8 (A 8)DB 3 (PMR 3) 1 (PMR)Too young 4 (A 1, SMR 1)f 3g

Cognitive levelh

A 9 1 9NA 6 5 2MMR 3 10 4SMR 5 3 3PMR 9 2Too young 2 3

Visual impairmenti No subjects with PSVI/SVI. 19/31 6/20VI Data on number of sub-

jects with VI not available.2 4

PSVI 8SVI 9 2

Hearing impairmentj 5/19 31/31 16/20Bilateral Data on severity of hear-

ing impairment not avail-able.

31 12

Minor 7 2Moderate 1 5Severe 23 5

Unilateral 4Minor 4

a Five out of those 21 diagnosed as regards ASCs were previously reported by Gillberg and Steffenburg (1989).b One out of those diagnosed as regards ASCs was previously reported by Fernell et al. (1999).c One out of those 19 diagnosed as regards ASCs was previously reported by Landgren et al. (1992).d ASCs: autism spectrum conditions; ALC: autistic-like condition; AT: autistic traits; AT?: autistic traits?; DB: deafblind.e Cognitive level is given for each individual within each diagnostic category.f Two individuals were too young to be assessed regarding cognitive level.g Three individuals were too young to be assessed regarding cognitive level.h A: average intelligence (IQ!85); NA: near average intelligence (IQ 7084); MMR: mild mental retardation (IQ 5069); SMR: severemental retardation (Mobius study: IQ

DISCAPACIDAD INTELECTUAL

La inteligencia suele ser normal DI LEVE Aprox. el 10-15% de los pacientes

Muchos autores sealan que sin pruebas formales, la inteligencia puede estar subes.mada debido a la apariencia facial del paciente

Verzijl et al no encontr ninguna disminucin en el CI, capacidad de concentracin o de memoria en 12 adultos con SM, en comparacin con la poblacin sana

SNDROME DE MOEBIUS


J Neurol. 2005 Feb;252(2):202-7.

Cognitive evaluation in children and adolescentswith Mbius sequence

W. Briegel, M. Schimek, D. Knapp, R. Holderbach, P. Wenzel and E.-M. Knapp

Department of Child and Adolescent Psychiatry and Psychotherapy, Leopoldina Hospital, Schweinfurt, Germany

Accepted for publication 7 December 2008

Keywordschildren and adolescents,intelligence, mentalretardation, Mbiussequence

Correspondence:Dr Wolfgang Briegel,Klinik fr Kinder- undJugendpsychiatrie undPsychotherapie,Leopoldina Krankenhaus,Gustav-Adolf-Strae 4,97422 Schweinfurt,GermanyE-mail:[email protected]

AbstractBackground Mbius sequence is a rare condition usually defined as uni- or bilateral congenital

facial weakness with impairment of ocular abduction. Mental retardation is estimated to occur in

1015% of cases, but at present there have been no studies focusing on the intellectual capacities

of children and adolescents with Mbius sequence.

Methods Twenty-three children and adolescents aged 616 years could be recruited following a

request of the German Mbius foundation. The primary caregivers of all subjects filled out a special

questionnaire to compile personal, somatic and psychosocial history of the probands. All subjects

had a physical examination. To assess intellectual capacities, the German version of the Wechsler

Intelligence Test-III (WISC-III) was administered. In case of a severe mental retardation, the Vineland

Adaptive Behavior Rating Form was used as an alternative.

Results Twenty-two subjects [12 males, 10 females; mean age: 11.3 (616) years] could be

included; 21 could be examined with the WISC-III. Compared with the normative sample, Full Scale

IQ (mean: 92.05; standard deviation: 14.84) was significantly lower (P = 0.023) which was theconsequence of a very low Performance IQ (mean: 80.48; standard deviation: 15.84). Compared with

the normative sample, the results of all performance subtests were significantly lower

(P = 0.0330.000), whereas verbal subtest scores did not differ or were even higher [Similarities(P = 0.026) and Vocabulary (P = 0.019)]. Verbal IQ (mean: 106.24; standard deviation: 15.31) was notsignificantly different from the normative sample. Two boys met ICD-10 criteria for mental

retardation. Full Scale IQ was not predictive for academic success.

Conclusions The WISC-III is not an adequate predictor for academic success in Mbius patients;

intelligence tests which are less dependant on time constraints should be preferred for subjects

with Mbius sequence.

Introduction

Mbius syndrome (OMIM no. 157900), or better Mbiussequence, is a rare, non-progressive congenital conditionwith a prevalence of 0.00020.002% of births (Kuklik 2000;Verzijl et al. 2003). In most studies, Mbius sequence hasbeen defined as a congenital facial weakness with congenitalimpairment of ocular abduction (Meyerson & Foushee 1978;

Cronemberger et al. 2001; Bandim et al. 2003; Verzijl et al. 2005;Briegel 2007).

Owing to mask-like facies, drooling saliva, strabism andspeech difficulties children with Mbius sequence are at riskto be misdiagnosed as mentally retarded (Kumar 1990). Thetrue incidence of mental retardation in patients with Mbiussequence is difficult to determine, as there is a considerablerange in different studies (Amaya et al. 1990; Ghabrial et al.

Child: care, health and developmentOriginal Article doi:10.1111/j.1365-2214.2009.00943.x

2009 The AuthorsJournal compilation 2009 Blackwell Publishing Ltd650

23 pacientes, 6-16 aos Se aplic la versin alemana del WISC-III En caso de DI severa Escala de

Vineland

Journal compila.on 2009 Blackwell Publishing Ltd, Child: care, health and development, 35, 5, 650655

practically and theoretically oriented students for trade, techni-cal and administrative professions, and Gymnasium as aca-demic secondary school, preparing students to tertiaryeducation or university. Seven children or adolescents went toGymnasium, and two to Realschule. All subjects who attendedGymnasium made good grades, and none of them receivedspecial assistance at school. Additionally, two subjects attendeda school specialized in providing education for students withspecial needs with one of them attending a school for mentallyretarded students.

Four subjects had already been seen by a child and adolescentpsychiatrist. Two children had attention deficit/hyperactivitydisorder and were medicated with methylphenidate, one subjectsuffered from social phobia (no medication), and one subjecthad no ICD-10 diagnosis. Another child was treated with lam-otrigine because of seizures.

Intellectual performance

Intelligence assessment took about 2 h and was performed inthe morning.

One boy, aged 11 years, could not be examined with theWISC-III as he was both mentally and physically severely handi-

capped. Therefore, the Vineland Adaptive Behavior RatingForm was administered with the following results: communica-tion domain: standard score 26, age equivelant 2 years, 1 m;daily living skills domain: standard score below 20, age equiva-lent 2 years, 1 m; socialization domain: standard score 40,age equivalent 2 years, 0 m; adaptive behaviour composite:standard score 26, percentile

EXAMEN FSICO

Los hallazgos {sicos dependen de la definicin de caso del SM Al u.lizar la definicin ms comnmente aceptada, la apariencia qpica fenoqpica es un aspecto de cara hipommica con diversas parlisis de la mirada

SNDROME DE MOEBIUS

FACIE DE MSCARA

Dificultades para relacionarse con otras personas

Parlisis de oculares externos, incluyendo ptosis 80% de los pacientes ConjunHviHs recurrente o crnica Opacidades corneales inusuales Disfagia comn

EXAMEN FSICO

Anomalas menos frecuentes: Dextrocardia, artrogriposis mlHple congnita Alt. de la piel: Pigmentacin caf-au-lait, ausencia de tejido subcutneo

Un caso con parlisis cordal bilateral congnita fue reportado por Kanemoto en 2007

SNDROME DE MOEBIUS

Eur J Pediatr. Aug 2007;166(8):831-3.

PARLISIS DEL NERVIO ABDUCENS

Parlisis del VI PC se presenta en aprox. el 75% de los pacientes

La mayora bilateral y generalmente completa Es la nica parlisis ocular en aprox. el 50% de los pacientes Los nios afectados pueden nacer con un estrabismo convergente marcado

SNDROME DE MOEBIUS

SNDROME DE MOEBIUS

tional lacrimation (most cases) to tearing while eating (crocodiletears). In all cases, a late onset of lacrimation (between 4 and 6months) was reported.

Visual Acuity, Refraction Defects, and SensoryVisual Function

Best-corrected visual acuity was not detectable in 17 patients(37%) who were too young; however, their cycloplegic retinos-copy showed no significant refractive defects. In the measured 29cases, the logarithm of the minimum angle of resolution value wasat least 0.3, without evidence of refractive errors. Binocular func-tion was tested in 31 of 46 patients, all of them showing a completeabsence of stereopsis with suppressive scotoma.

Biomicroscopy and Funduscopic Features

Eyelid examinations revealed canthal and interpupillary distancesto be within normal limits in all cases. Epicanthal folds were foundin 7 patients (15%), and ptosis was found in 2 cases (4%). Thirty-five patients (76%) had epiphora with a patent lacrimal drainagesystem (resulting from a lacrimal pump defect related to the facialcranial nerve palsy). Slit-lamp biomicroscopy and indirect oph-thalmoscopy were unremarkable in all cases.

Discussion

Documents

HOSPITALC LÍNICOS ANB ORJAA RRIARÁN SERVICIO DEN ... · SÍNDROME)DE)MOEBIUS) HOSPITALC LÍNICOS ANB ORJAA RRIARÁN) SERVICIO)DEN EUROPSIQUIATRÍAI NFANTIL! Dr.GuillermoFariñaKutz