Molecular and neuroimaging findings in pontocerebellar hypoplasia type 2 (PCH2): Is prenatal diagnosis possible?

John M. Graham, Andrew H. Spencer, Inessa Grinberg, Charles E. Niesen, Lawrence D. Platt, Marcel Maya, Yasmin Namavar, Frank Baas, William B. Dobyns

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20 Scopus citations


The pontocerebellar hypoplasias (PCH) are a group of early-onset, autosomal recessive disorders resulting in abnormal growth and function of the brainstem and cerebellum. PCH type 2 (PCH2) is characterized by respiratory and feeding difficulties at birth, extrapyramidal dyskinesia, severe developmental impairment, progressive microcephaly and frequent death in childhood. Neuropathologic findings include diffuse cerebral gliosis with white matter changes, hypoplastic pons with depletion of neurons in the pontine nuclei, hypoplastic cerebellar hemispheres due to short cerebellar folia with poor branching, segmental loss of dentate, inferior olivary, and ventral pontine nuclei, and near absence of transverse pontine fibers with preservation of long fiber tracts and spinal anterior horn cells. On brain imaging, the cerebellar hemispheres appear very flat, and are more severely involved than the vermis. Most patients with PCH2 have mutations in TSEN54, with occasional mutations found in TSEN34 or TSEN2, genes that encode subunits of tRNA splicing endonuclease. Although this is a congenital disorder of pontocerebellar dysgenesis with fetal onset of neurodegeneration and symptoms at birth, prenatal imaging is unreliable in diagnosing this disorder in utero. We report on IVF dizygous twins with detailed prenatal imaging that failed to reveal any cerebellar abnormalities. Direct sequence analysis of TSEN54 showed homozygosity for c.919G>T, the common founder mutation in most PCH2 patients, and both parents were heterozygous for this mutation. We found no evidence of cerebellar dysgenesis on prenatal ultrasounds, but MRI tractography showed absence of pontine crossing fibers, a unique feature that might be useful for prenatal diagnosis of this condition.

Original languageEnglish (US)
Pages (from-to)2268-2276
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Issue number9
StatePublished - Sep 2010
Externally publishedYes


  • Autosomal recessive
  • Cerebellar hypoplasia
  • Dyskinesia
  • Microcephaly
  • Neurogenetics
  • Neuroimaging
  • Prenatal diagnosis
  • TSEN54 mutation
  • tRNA-splicing endonuclease


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