Large interstitial duplication in the LARGE-gene in a patient with Walker-Warburg-syndrome.

Mutations in the LARGE gene are a rare condition causing Walker-Warburg-syndrome and other forms of a-dystroglycanopathies. We report on a girl with clinical features of Walker-Warburg Syndrome – the most severe form of a-dystroglycanopathy. We found an interstitial amplification (4 copies) of a 132 kb segment within the LARGE-Gen by 6.0 SNP-Array analysis. The 19 month old girl suffers from very severe global developmental delay and severe hypotonia. She is not able to turn her head or move any part of her body. She has got brain malformations including large dilatation of the supratentoral ventricle system with monoventriculare configuration of lateral ventrikels and missing septum, pachymicrogyria, agenesis of dorsal corpus callosum, aquaduct stenosis and hydrocephalus occlusus, cerebellar vermis agenesy of the caudal part. She has got microphthalmy and cataract at the left eye and proximale ureter stenosis (Ureterabgangsstenose) with hydronephrosis. She started myoclonic seizures at the age of 6 weeks. CK was highly elevated (>2000U/l). The parents are first cousins. This is first case of Walker-Warburg Syndrome caused by a large interstitial duplication in the LARGE-gene.