Brain MRI abnormalities in muscular dystrophy due to FKRP mutations

Brain Dev. 2006 May;28(4):232-42. doi: 10.1016/j.braindev.2005.08.003. Epub 2005 Dec 20.

Abstract

Introduction: FKRP mutations cause a muscular dystrophy which may present in the neonatal period (MDC1C) or later in life (LGMD2I). Intelligence and brain imaging have been previously reported as being normal in FKRP-associated muscular dystrophy, except in rare cases presenting with mental retardation associated with structural brain abnormalities.

Patients and methods: We studied cerebral MRIs in twelve patients with FKRP-associated muscular dystrophy presenting in infancy or early childhood, at ages between 14 months and 43 years. Two patients had severe cognitive deficits, four had mild-moderate mental retardation and the rest were considered to have normal intelligence. All, but one were wheelchair-bound and 7 were mechanically ventilated.

Results: Brain MRI was abnormal in 9 of 12 patients. Brain atrophy was seen in 8 patients. One child had isolated ventricular enlargement at 4 years. Cortical atrophy involved predominantly temporal and frontal lobes and was most important at later ages. In two cases with serial images this atrophy seemed progressive. Three patients, two with severe and one with moderate mental retardation, showed structural abnormalities of the posterior fossa with hypoplasia of the vermis and pons, and cerebellar hemispheric cysts. These abnormalities were stable with time. Two of these three patients also showed diffuse white matter abnormalities in early childhood, which regressed with time.

Conclusions: MRI abnormalities are common in patients with FKRP-associated muscular dystrophy presenting at birth or in early childhood. Progressive brain atrophy is the most frequent finding. Posterior fossa malformations and transient white matter changes may be seen in patients with associated mental retardation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Atrophy / genetics
  • Atrophy / pathology
  • Brain / abnormalities*
  • Brain / pathology
  • Child
  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Muscular Dystrophies / complications*
  • Muscular Dystrophies / genetics*
  • Mutation / genetics*
  • Nervous System Malformations / genetics*
  • Pentosyltransferases
  • Proteins / genetics*

Substances

  • Proteins
  • FKRP protein, human
  • Pentosyltransferases