Morphology of the facial motor nuclei in a rat model of autism during early development.

The development of facial nuclei in animal models of disease is poorly understood, but autism is sometimes associated with facial palsy. In the present study, to investigate migration of facial neurons and initial facial nucleus formation in an animal model of autism, rat embryos were treated with valproic acid (VPA) in utero at embryonic day (E) 9.5 and their facial nuclei were analyzed by in situ hybridization at E13.5, E14.5 and E15.5. Signals for Tbx20, which is expressed in early motor neurons, appeared near the floor plate at the level of the vestibular ganglion and extended caudolaterally, where they became ovoid in shape. This pattern of development was similar between control and VPA-exposed embryos. However, measurements of the migratory pathway and the size of the facial nuclei revealed that exposure to VPA hindered the caudal migration of neurons to the facial nuclei. Signals for cadherin 8, which is expressed in mature facial nuclei, revealed that exposure to VPA caused a significant reduction in the size of the facial nuclei. Our findings provide the first quantitative description of tangential migration and nucleus formation in the developing hindbrain in a rat model of autism.

Prenatal sonographic evidence supporting an in utero developmental etiology of Möbius sequence.

Möbius sequence features masklike facies with sixth and seventh nerve palsy and frequently micrognathia thought to result from a neuromuscular deficiency in early movement of the mandible. Failure to thrive in infancy is commonly due to feeding and aspiration difficulties. We present the first description of prenatal sonographic findings associated with this lesion, which also support an in utero developmental etiology of this rare condition.

Möbius sequence: further in vivo support for the subclavian artery supply disruption sequence.

Möbius sequence consists of a congenital bilateral facial nerve palsy and external ophthalmoplegia often associated with malformations of the limbs and orofacial structures. The pathogenesis of the sequence is a subject of debate. However, a new hypothesis proposes that Möbius sequence results from an interruption of embryonic blood supply (subclavian artery supply disruption sequence). Here we present an infant with bilateral facial nerve palsy (VII), external ophthalmoplegia (IV, VI), paresis of cranial nerves V, IX, X, XI, and XII, absence of the pectoralis major muscle (Poland anomaly), terminal transverse limb defects, and absence of the right diaphragm. Also, he was found to have discrete foci of brainstem calcifications in the region of the dorsal respiratory group on both CT scan and the histologic sections with microscopic evidence of diffuse brainstem "injury." The anomalies and histopathology noted in this infant imply that vascular insufficiency prior to the sixth week of gestation involving the proximal sixth intersegmental artery may result in the manifestations presented in this report and lend further support for the existence of a subclavian artery supply disruption sequence.

The development of facial muscles and nerves in relation to the Möbius syndrome.

This paper discusses descriptive and experimental embryologic material that may be of relevance in understanding the pathologic findings of, and attempting treatment of, congenital facial paralysis. The embryology of the human facial nerves and muscles is described. In experimental animals muscles undergo early stages of morphogenesis and differentiation in the absence of nerves and then undergo gradual atrophy. In th absence of muscle fibers, the bulk of embryonic motor nerves that would normally innervate the muscle die.

Mobius syndrome and limb abnormalities.

Most ophthalmologists are aware of the cranial nerve dysfunctions that have been associated with the facial diplegias of Mobius syndrome. However, many are not aware of the combined limb deficiencies and cranial nerve dysfunctions. Limb malformations have been associated with a spectrum of oral facial anomalies consisting of micrognathia, hypoglossia, microstomia, hypodontia, oral bands, and dysarthria. It has been suggested that the differences which exists between these entities may in fact represent a common etiology. The variability may be related to an intrauterine insult at slightly different times. The oral-facial anomalies associated with absence of limbs or of limb anomalies suggests a correlation between the limbs and the first visceral arch possibly within the second month of gestation.