Abstract

DO.18.02

Exclusive and frequent appearance of the KIF21A variant R941W in familial and sporadic cases of congenital fibrosis syndrome of the extraocular muscles – CFEOM

Rudolph G.¹, Hellebran H.², Nentwich M.¹, Pollack K.³, Bau V.⁴, Gordes R.⁵, Boergen K.-P.¹, Mühlendyck H.⁵, Meindl A.^2
1Augenklinik der Ludwig-Maximilians-Universität München; ²Molekulargenetisches Labor, Frauenklinik der TU München; ³Augenklinik der Universität Dresden; ⁴Augenklinik der Universität Halle/Saale; ⁵Augenklinik der Georg August Universität Göttingen

Objective: To demonstrate the clinical characteristics and determine the mutation in the KIF21A-gene encoding a kinesin-motor protein in patients with CFEOM.
Methods: Clinical examination in five families met criteria of CFEOM, as well as two simplex cases. DNA was extracted directly from blood samples for moleculargenetic analysis. All 37 KIF21A exons and corresponding exon-intron boundaries were amplified by polymerase chain reaction from genomic DNA.
Results: The affected individuals were all born with a typically motility disorder with eyes fixed in downgaze and exo- or esotropia and severe limitation of excursions. Bilateraly ptosis was present in all individuals in a variable degree. Two of the sporadic cases and three index-patients out of five unrelated families diagnosed with CFEOM showed an identical recurrent mutation in exon 20 (R941W) of the KIF21A-gene, which confirms the disease. One child was diagnosed having Joubert syndrome. In one family no mutation was present.
Conclusions: CFEOM is characterized by variable gegree of restricted motility especially in upgaze. New insights in the mechanism of the disease has provided evidence that CFEOM results from a dysregulation in the development of the extraocular muscle motor neuron system. The hypothesis is supported by findings of moleculargenetic analysis, demonstrating mutations in the KIF21A motor protein gene.

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