Neurologic features of horizontal gaze palsy and progressive scoliosis with mutations in ROBO3

Abstract

The major clinical characteristics of horizontal gaze palsy and progressive scoliosis were congenital horizontal gaze palsy and progressive scoliosis with some variability in both ocular motility and degree of scoliosis. The syndrome also includes a distinctive brainstem malformation and defective crossing of some brainstem neuronal pathways.

Five new consanguineous families with horizontal gaze palsy and progressive scoliosis and novel ROBO3 mutations

“…These include nine missense/nonsense mutations, one splice site mutation, two small insertions, and two deletions. We describe here seven new patients with the typical HGPPS clinical presentation from five consanguineous families of Arabic origin with five novel homozygous ROBO3 mutations [3]. One patient clinically proves the uncrossed character of corticospinal tracts in HGPPS.…”

“…One of the most fascinating aspects of this syndrome is the fact that long motor and sensory tracts seem to be uncrossed by electrophysiologic [1] and anatomic [2][3][4] criteria. It is an autosomal recessive disorder caused by mutations in the ROBO3 gene on chromosome 11 [2].…”

Allelic ROBO3 Heterogeneity in Tunisian Patients with Horizontal Gaze Palsy with Progressive Scoliosis

“…None of these mutations have been reported previously except for the c.733C>T mutation which has been reported as a compound heterozygous with the c.2317C>T mutation (Chan et al 2006). Table 1 lists all previously reported mutations of ROBO3 associated with HGPPS (Bosley et al 2005;Abu-Amero et al 2009) together with the five mutations described here. These mutations are scattered throughout the ROBO3 gene without a specific region or domain that can be considered a hot-spot area for mutations.…”

“…Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare autosomal recessive disorder characterized by the absence of conjugate lateral eye movements with preserved vertical gaze and progressive scoliosis from birth (Bosley et al 2005). A striking brainstem malformation, with markedly diminished size and a bifid appearance of the medulla oblongata ("butterfly medulla"), is found in patients with HGPPS (Jen et al 2004;MacDonald et al 2004).…”

Recessive Mutations in COL25A1 Are a Cause of Congenital Cranial Dysinnervation Disorder

“…1 Most CCDDs present with abnormal ocular motility; these include congenital fibrosis of the extraocular muscles type [2][3][4][5][6][7] Mutations in different genes contribute to CCDD etiology by affecting neuronal development. Expressions of certain genes influence the development of the cranial nerves through molecular events including the cytoskeleton microtubule dynamics and axon path guidance.…”