receives nerve impulses of the third nerve, thus keeping the angle of squint in primary gaze relatively small with regard to the motility deficiency in abduction. Sometimes even overcompensation with a divergent angle in primary position or synergistic divergence on adduction occurs. The most common pattern of motility in Duane syndrome is an abduction deficiency, accompanied by a slighter adduction deficiency that results from the lateral rectus cocontracting on intended adduction. This cocontraction results in retraction of the globe and narrowing of the palpebral fissure on adduction.

Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS)

A disturbance in the SLIT/ROBO signaling pathway has been found out to be the cause of a complex CCDD that leads to a horizontal gaze palsy with una ected vertical eye movements. In the entity of so-called HGPPS hindbrain anomalies and ocular motor anomalies can be explained by disorders of the pathfinding of fibers that normally cross the midline in the hindbrain. Mutations in the ROBO3 gene that encodes a transmembrane receptor molecule that normally seems to promote midline crossing of some hindbrain axons were identified in patients with HGPPS [15, 45]. The neuroanatomic correlates for the typical eye motility pattern (Fig. 7.3) are not fully understood, special neuroradiologic techniques could show that the typical hypoplastic appearance of the hindbrain on conventional NMR goes along with noncrossing fibers of ascending and descending tracts [46–48]. Neurologic examinations confirm that atypical lack of crossing fibers exists [49]. The nature of the progressive scoliosis which means a significant impairment to the patients may be to be neurogenic.

a

b

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7.1.1.3Disorders Understood as CCDDs

The pathophysiological concept of CCDDs also helps to understand other congenital, nonprogressive disorders and syndromes in which the proper motor innervation of cranial muscles is lacking, deficient or substituted. Such syndromes in which the causative mechanism is not yet fully understood encompass disturbances in the third, fourth, sixth and seventh cranial nerves.

Congenital ptosis is a part of the features of CFEOM and in this context proven to be a CCDD. As an isolated trait it is in some forms also presumed to represent a minor variant of dysinnervation in the target area of the third nerve. Familial cases hint to genetic causes and gene loci already have been identified.

Fig. 7.3 Patient with familial horizontal gaze palsy and progressive scoliosis (HGPPS). Patient after bilateral medial rectus recession for esotropia. Fixation in primary gaze with binocular functions (c). Only slight adduction movements on intended right (b) and left (d) gaze. Unimpaired elevation (a) and depression (e)

Congenital synkinetic movements of the lid on jaw movements often with congenital ptosis are referred to as Marcus Gunn phenomenon and hint to a paradoxical innervation in the levator palpebrae by fibers of the motor portion of the fifth nerve (Fig. 7.4). Misrouting of sixth and seventh nerve fibers into the levator palpebrae also has been described [28, 47, 50, 51]. One of our patients

displays lid opening on intended downgaze on adduction, hinting to a possible miswiring of fourth nerve neurons in this case (Fig. 7.5).

Congenital fourth nerve palsy may represent a CCDD with only primary dysinnervation resulting in elevation of the eye on adduction and reduced depression on adduction (Fig. 7.6). The disorder was put into the context with

CCDDs by Traboulsi [52, 53]. Familial cases are described [54, 55] but an associated gene locus is not yet identified. In a study targeting on ARIX as a candidate gene in congenital trochlear palsy, no mutation was identified yet the authors hint to a high rate of polymorphisms [55]. Synkinetic movements of the superior oblique on mouth opening and swallowing have been described [47].