MOEBIUS SYNDROME ASSOCIATED WITH EXPOSURE TO MISOPROSTOL

JC Martin S.Cabrera, MD Bibhuti R.Thapa, MD Emilio L. Macias III, MD Evelyn S. Morabe,MD

DEPARTMENT OF OPHATHALMOLOGY JOSE R. REYES MEMORIAL MEDICAL CENTER San Lazaro Compound, Rizal Avenue, Sta. Cruz, Manila, Philippines

No financial assistance was received for this case report The authors have no financial interest for this case report

Correspondence to: JC Martin S. Cabrera, MD # 1321 Quintos Sr. St., Sampaloc, Manila, Philippines 09228000712 jcmartins.cabrera22@yahoo.com

Keywords: Moebius syndrome, Misoprostol, Strabismus. Pediatric ophthalmology, drug exposure

ABSTRACT Moebius syndrome is a rare condition characterized by the association of both VI and VII cranial nerve palsies, the latter causing mask like facies. Many patients also show limb, chest and tongue defects. The etiopathogenesis of Mbius sequence is still unclear. Although the genetic etiology is the most accepted, environmental causes have been proposed because of the increasing number of cases associated with the use of misoprostol during pregnancy .We demonstrated a 8 years old boy presented with inward deviation of left eye since birth associated with deviation of mouth and incomplete closure of left eyelid. On examination, bilateral restriction of abduction of both eyes was found with other non ophthalmologic findings like deviation of tongue to left on protusion , bilateral club foot and mask like face. Maternal history was positive for oral intake of 1 tablet of Misoprostal during first trimester as abortificient. OBJECTIVE To discuss and help in recognition of a rare developmental anomaly. To report a case of child, born with Moebius Syndrome following exposure in utero to misoprostol for elective abortion.

METHOD A case report

CASE An 8 years old boy, born full term by NSD to 21years old primigravid at health center delivered by midwife with-out any fetomaternal complications. At 3 months age of gestation, the mother attempted abortion with misopro-stol taking 1 tablet orally. At birth, deviation of the eyes was noted. At 1 year of age, deviation of mouth with incomplete closure of left eye was noted. Patient had normal growth but delay in development of speech. On ophthalmologic examination, VA was 20/50 -> 20/25 on right, 20/160 -> 20/63 on left eye. Restriction of movement of eye laterally on both eyes was noted. Lagophthalmos, bilateral epicanthal folds with microcornea of left eye was observed. On slit lamp examination, positive punctuate epithelial dye uptake was present. Fundus examination was normal. Krimsky test on Right eye fixating was 35 prism diopter LHT and on cover uncover test, 35LHT on primary gaze, 20RET on right gaze and 45LHT with 50LET on left gaze was found. Atropine refraction was+ 2.50 diopter sph -1.50 diopter cyl X180 on right eye and +4.50 diopter sph - 1.00 diopter cyl X180 on left eye. Amblyopia in this patient was most probably due to strabismus and anisometropia. Other non ophthalmologic findings were deviation mouth with deviation of tongue on protusion, and could not properly smile causing mask like face and club foot. Eye glasses was provided which improved the visual acuity to 20/32 on right eye and 20/100 on left eye. Symptomatic treatment was done with ointments and eye patching started. Patient was suggested for regular followup and muscle surgery was planned.

CASE DISCUSSION In the clinical setting, the findings like various gaze palsies, associated with mask-like facies, incomplete eyelid closure, deviation of mouth and tongue, and speech impairment raises a high index of suspicion for Mbius syndrome, a disorder primarily involving the facial and abducens motor nerves. Ocular conditions that may present with with limited lateral rectus function include congenital sixth-cranial-nerve palsy, and Duane syndrome. These conditions, however, do not have signs and symptoms characteristic of facial nerve involvement. Facial nerve involvement with deviation of mouth can be seen in Assemetric crying facies but doesnt have any ocular involvement. All these ocular and non-ocular findings can be seen in Mbius syndrome. Von Graefe initially described a patient with congenital facial diplegia in 1880 but Paul Julius Mbius, a German neurologist, reviewed more cases and reported an association with congenital, nonprogressive bilateral facial and abducens nerve palsy along with other systemic abnormalities.Later, Verzijl suggested facial palsy with impairment of ocular abduction as the primary criterion for Mbius syndrome. The etiology of Mbius syndrome is multifactorial, and several theories have been proposed, with the most supported theory being that of transient ischemic or hypoxic insult to the fetus. Other infectious and genetic etiologies have also been proposed. In addition, the use of misoprostol, a prostaglandin-E1 analog and abortifacient during pregnancy, has also been implicated. Misoprostol is a synthetic prostaglandin E analogue with greater antisecretory and mucosal-protective activity than natural prostaglandins. It is used to prevent and treat gastrointestinal lesions induced by nonsteroidal antiinflammatory drugs and upper gastrointestinal ulceration. It is not recom- during early pregnancy, because it may mended stimulate uterine contractions and cause vaginal bleeding, which may endanger fetal survival. Misoprostol has been used for the elective induction of abortion. Congenital defects following prenatal exposure in early pregnancy to misoprostol include skull defects, bladder exstrophy, arthrogryposis, cranial nerve palsies, facial malformations, terminal transverse limb defects, and Moebius sequence. Mbius syndrome is congenital, non progressive .No definitive treatment available. Nonsurgical ophthalmologic management include early detection and treatment of amblyopia giving best correction and symptomatic treatment. Amblyopia in these patient might be due to strabismus or anisometropia. There is no single surgical approach to correct strabismus of patients with Mbius sequence, though muscles recessions and transpositions can be the option. treatment for facial nerve palsy involves reconstructive plastic surgery with muscle transplantation ideally performed in patients just before they reach school age at 4 or 5 years. CONCLUSION 1. We therefore conclude that the public should be educated on the potential teratogenic effects of misoprostol in order to eliminate its use as an abortifacient. Awareness about this syndrome for early diagnosis and treatment of the patient is needed. Parents counseling and education are invaluable.