A Second Gene for Autosomal Dominant Möbius Syndrome Is Localized to Chromosome 10q, in a Dutch Family

Abstract

Möbius syndrome (MIM 157900) consists of a congenital paresis or paralysis of the VIIth (facial) cranial nerve, frequently accompanied by dysfunction of other cranial nerves. The abducens nerve is typically affected, and often, also, the hypoglossal nerve. In addition, orofacial and limb malformations, defects of the musculoskeletal system, and mental retardation are seen in patients with Möbius syndrome. Most cases are sporadic, but familial recurrence can occur. Different modes of inheritance are suggested by different pedigrees. Genetic heterogeneity of Möbius syndrome has been suggested by cytogenetic studies and linkage analysis. Previously, we identified a locus on chromosome 3q21-22, in a large Dutch family with Möbius syndrome consisting essentially of autosomal dominant asymmetric bilateral facial paresis. Here we report linkage analysis in a second large Dutch family with autosomal dominant inherited facial paresis. After exclusion of >90% of the genome, we identified the locus on the long arm of chromosome 10 in this family, demonstrating genetic heterogeneity of this condition. The reduced penetrance suggests that at least some of the sporadic cases might be familial.

Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve

“…It will therefore be interesting to determine if any of these genes are linked to the disease locus. Transient ischemia during hindbrain development may also contribute to Moebius syndrome (e.g., Verzijl et al 1999). As VEGF-A gene expression is regulated by hypoxia, defective VEGF signaling might contribute to the aetiology of sporadic Moebius cases by simultaneously disturbing hindbrain vascularisation and facial nerve development.…”

Refinement of the locus for hereditary congenital facial palsy on chromosome 3q21 in two unrelated families and screening of positional candidate genes

“…Linkage analysis in these two families identified two different loci cosegregating with the disorder, chromosome 3q21 -22 in HCFP1 and chromosome 10q21 -22 in HCFP2, 12,15 indicating genetic heterogeneity for this disorder.…”

“…Linkage analysis identified a locus on chromosome 10q21.3 -q22.1 cosegregating with the disorder. 15 Mutation analysis on the candidate genes EGR2, CTNNA3, and LRRTM3 located within or nearby the critical region failed to identify the underlying genetic defect for HCFP2 (B van der Zwaag, unpublished data). 20 For the smaller HCFP families, linkage analysis was not reported.…”

Congenital innervation dysgenesis syndrome (CID)/congenital cranial dysinnervation disorders (CCDDs)

“…68 Tischfield et al 46 reported horizontal gaze palsy and facial weakness in consanguineous patients with recessive HOXA1 mutations. However, in another pedigree study by Dumars et al 69 no mutations were detected in the genes PHOX2A, HOXA1, and KIF21A.…”