Pontocerebellar hypoplasia associated with respiratory-chain defects

Research output: Contribution to journalArticle


Pontocerebellar hypoplasias are congenital disorders of brain morphogenesis which include such diverse etiologies as carbohydrate-deficient glycoprotein syndrome type 1, cerebromuscular dystrophies (Walker-Warburg syndrome, Fukuyama syndrome, muscle-eye-brain disease) and at least two types of autosomal recessive neurodegenerations known as pontocerebellar hypoplasia type I and II. Pontocerebellar hypoplasia type 1 is a lethal phenotype and clinical features include congenital contractures, respiratory insufficiency, central and peripheral motor dysfunction and spinal anterior horn degeneration. Type 2 is characterized by progressive microcephaly, extrapyramidal dyskinesia and normal spinal cord findings. In this paper, we describe a girl, born at 33 weeks of gestation, presenting with respiratory insufficiency and multiple contractures. MRI scan of the brain demonstrated pontocerebellar hypoplasia and cortical and diffuse periventricular white matter abnormalities. Postmortem examination showed pontocerebellar hypoplasia with extensive gliosis of the periventricular white matter and of the basal ganglia with normal spinal cord findings. Histology of skeletal muscle was normal. Biochemical analysis demonstrated multiple deficiencies of respiratory chain enzymes in skin fibroblasts. This case demonstrates a lethal phenotype of pontocerebellar hypoplasia without spinal cord abnormalities associated with a respiratory-chain disorder. The diagnostic workup in a patient whose brain image shows pontocerebellar hypoplasia should include a search for respiratory-chain impairment.


  • T. J. De Koning
  • L. S. De Vries
  • F. Groenendaal
  • W. Ruitenbeek
  • G. H. Jansen
  • B. T. Poll-The
  • P. G. Barth
External organisations
  • Wilhelmina Children’s Hospital
  • University Medical Center Utrecht
  • Radboud University Medical Center
  • Academic Medical Center of University of Amsterdam (AMC)
Research areas and keywords


  • Fetal onset, Pontocerebellar hypoplasia, Respiratory chain defects
Original languageEnglish
Pages (from-to)93-95
Number of pages3
Issue number2
Publication statusPublished - 1999 Jan 1
Publication categoryResearch
Externally publishedYes