title: A new type of leukoencephalopathy with metaphyseal chondrodysplasia maps to Xq25-q27.
abstract: BACKGROUND
  The authors report a three-generation family with four male patients presenting with a novel type of X-chromosomal leukoencephalopathy associated with skeletal abnormalities.
  
  
  METHODS
  The index patient and his brother reached their early motor milestones in due time and had normal language development. Between the ages of 2 and 3 years, first signs of spastic paraplegia were noticed. Furthermore, the patients developed tremor, ataxia, optic atrophy, and spastic tetraparesis. Both boys had broad wrists and knees without significant contractures. A maternal uncle and a granduncle had the same disease.
  
  
  RESULTS
  Leukoencephalopathy (MRI, MRS) and metaphyseal chondrodysplasia (X-ray, MRI) were diagnosed. MRS showed a reduction of choline-containing compounds in the white matter. An autopsy on one of the patients, who died at age 37 years, revealed an orthochromatic type of leukoencephalopathy. In bone and cartilage tissue, unspecific signs of a mild chondrodysplasia were found. At the PLP gene locus an obligate recombination was observed, which excludes the Pelizaeus-Merzbacher locus on Xq21-22. However, affected males share a fragment of the long arm of chromosome X.
  
  
  CONCLUSIONS
  The authors report a new type of leukoencephalopathy associated with metaphyseal chondrodysplasia located on Xq25-q27.
authors.affiliation: Department of Pediatric Neurology, Universities of Giessen. Bernd.A.Neubauer@paediat.med.uni-giessen.de
authors.forename: B A
authors.initials: BA
authors.lastname: Neubauer
authors.forename: I
authors.initials: I
authors.lastname: Stefanova
authors.forename: C A
authors.initials: CA
authors.lastname: Hübner
authors.forename: E
authors.initials: E
authors.lastname: Neumaier-Probst
authors.forename: J
authors.initials: J
authors.lastname: Bohl
authors.forename: H C
authors.initials: HC
authors.lastname: Oppermann
authors.forename: H
authors.initials: H
authors.lastname: Stö
authors.forename: A
authors.initials: A
authors.lastname: Hahn
authors.forename: U
authors.initials: U
authors.lastname: Stephani
authors.forename: A
authors.initials: A
authors.lastname: Kohlschütter
authors.forename: A
authors.initials: A
authors.lastname: Gal
mesh_terms: D000328:Adult; D001927:Brain Diseases / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D010009:Osteochondrodysplasias / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree