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.
