MOEBIUS SYNDROME DUE TO PRENATAL EXPOSURE TO MISOPROSTOL

BIBHUTI R. THAPA, MD; EMILIO L. MACIAS III, MD; EVELYN S. MORABE, MD; MA. LOURDES NANAGAS, MD DEPARTMENT OF OPHATHALMOLOGY JOSE R. REYES MEMORIAL MEDICAL CENTER, MANILA, PHILIPPINES

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. KEY WORDS: Moebius syndrome, Misoprostol.

INTRODUCTION: 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. 1 out of every 50,000 live births is found to have moebius syndrome. Mbius syndrome is characterized by unilateral, mostly bilateral palsy of the abducens (VI) and facial (VII) cranial nerves. Other cranial nerves (eg, the hypoglossal (XII), craniofacial or orofacial anomalies, and limb malformations are often associated. The etiology of the Mbius syndrome remains largely unknown and probably involves multiple factors. The most likely etiological hypothesis is disruption of the developing vascular system, with transient ischemia

METHOD: A case study

(particularly in the vertebral arteries) and fetal hypoxia. A teratogenic cause of Mbius syndrome has been suggested. The critical period for the development of Mbius syndrome following teratogen exposure appears to be 58 weeks of gestation. The oral or vaginal misoprostol administration can lead to a significant increase in Doppler-measured uterine artery resistance and may induce uterine contractions. If these occur during the critical embryonic period, they may cause flexion in the areas of the sixth and seventh cranial nerves and decreased blood flow. CASE REPORT: An 8 years old boy, born full term by NSD to 21years old primigravid at health center delivered by midwife without any fetomaternal complications. At 3months age of gestation, the mother attempted abortion with misoprostol , 1 tablet orally. At birth, deviation of the eyes was noted. At 1year 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, 35 LHT on primary gaze, 20 RET on right gaze and 45 LHT with 50LET on left gaze was found. Atropine refraction was + 2.50diopter sph 1.50 diopter cyl X180 on right eye and +4.50diopter sph - 1.00 diopter cyl X180 on

left eye. Other non ophthalmologic findings were deviation of 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 follow up and muscle surgery was planned. DISCUSSION: In the clinical setting, the findings 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. Several diagnostic criteria since then have been proposed. The latest was by Verzijl who 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. In Brazil, where elective abortions are prohibited, 57 to 75 percent of women who attempt abortion use misoprostol. However, misoprostol often fails to induce abortion during the first trimester, and up to 80 percent of the pregnancies in women who use this agent continue to term. The research done at Brazil from the year the 1990 to 1996 showed, among the mothers of the 96 infants with Mbius syndrome, 47 (49 percent) had used misoprostol in the first trimester of pregnancy. A history of prenatal misoprostol exposure in Mbius sequence has been reported in 18.8% of patients as per research done at UP PGH. Out of 11 moebius patient 4 patients had prenatal misoprostol exposure from year 2005 to 2011.

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. In conclusion, the public should be educated on the potential teratogenic effects of misoprostol in order to reduce its use as an abortifacient. Awareness about this syndrome for early diagnosis and treatment of the patient is needed. Women with ongoing pregnancy after failed abortion with misoprostol administration should be informed of this risk. Parents counseling and education are invaluable. References: 1. American Academy of Ophthalmology, Pediatric ophthalmology and strabismus .Section VI (2010-2011). 2. Philippine Journal Of Ophthalmology Janjune 2011. 3. The New England Journal of Medicine.