A case of cerebral hypomyelination with spondylo-epi-metaphyseal dysplasia

Am J Med Genet A. 2013 Jan;161A(1):203-7. doi: 10.1002/ajmg.a.35686. Epub 2012 Dec 13.

Abstract

We reported on a male patient with rare leukoencephalopathy and skeletal abnormalities. The condition was first noticed as a developmental delay, nystagmus and ataxia at 1 year of age. At 4 years of age, he was diagnosed as hypomyelination with skeletal abnormalities from clinical features, brain magnetic resonance imaging (MRI) and skeletal X-rays. His brain MRI revealed diffuse hypomyelination. These findings suggested the classical type of Pelizaeus-Merzbacher disease (PMD) caused by proteolipid protein (PLP)-1 gene or Pelizaeus-Merzbacher-like disease (PMLD). However, we found neither mutation nor duplication of PLP-1. The patient had severe growth retardation and general skeletal dysplasia compatible with spondylo-epi-metaphyseal dysplasia; however the mutation of discoidin domain receptor (DDR) 2 gene was absent. The co-morbidity of hypomyelination with skeletal abnormalities is rare. We performed array CGH and no causal copy number variation was recognized. Alternatively, this condition may have been caused by a mutation of the gene encoding a molecule that functions in both cerebral myelination and skeletal development.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Transport Systems, Acidic / deficiency
  • Amino Acid Transport Systems, Acidic / genetics
  • Antiporters / deficiency
  • Antiporters / genetics
  • Brain Stem / abnormalities
  • Brain Stem / pathology
  • Child
  • Child, Preschool
  • DNA Copy Number Variations
  • Discoidin Domain Receptors
  • Hereditary Central Nervous System Demyelinating Diseases / diagnosis
  • Hereditary Central Nervous System Demyelinating Diseases / genetics*
  • Humans
  • Image Processing, Computer-Assisted
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Microarray Analysis
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / genetics*
  • Mutation
  • Myelin Proteolipid Protein / genetics
  • Osteochondrodysplasias / diagnosis
  • Osteochondrodysplasias / genetics*
  • Pelizaeus-Merzbacher Disease / diagnosis
  • Pelizaeus-Merzbacher Disease / genetics
  • Psychomotor Disorders / diagnosis
  • Psychomotor Disorders / genetics*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptors, Mitogen / genetics

Substances

  • Amino Acid Transport Systems, Acidic
  • Antiporters
  • Myelin Proteolipid Protein
  • Receptors, Mitogen
  • Discoidin Domain Receptors
  • Receptor Protein-Tyrosine Kinases

Supplementary concepts

  • Hypomyelination, Global Cerebral
  • Pyle disease