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

Abstract

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.

TSEN54 Gene-Related Pontocerebellar Hypoplasia Type 2 Could Mimic Dyskinetic Cerebral Palsy with Severe Psychomotor Retardation

“…Atrophy of the cerebral hemispheres is also found and may erroneously be interpreted as a result of hypoxic–ischemic pre- and/or perinatal brain injury. MR tractography shows almost full absence of transverse pontine crossing fibers and this could be additional finding in favor of PCH 2 ( 12 ).…”

X-ray 3D imaging of gene expression in whole-mount murine brain by microCT, implication for functional analysis of tRNA endonuclease 54 gene mutated in pontocerebellar hypoplasia

“…PCH is a heterogeneous group of autosomal recessive neurodegenerative disorders characterized by a wide diagnostic spectrum including the delay in cognitive and motor development, seizures and, death in early childhood (30). PCH subtypes morphologically characterized by severity of cerebellum and ventral pons hypoplasia, progressive microcephaly, neocortical atrophy (32).…”

Pontocerebellar hypoplasia: clinical case and literature review

“…dif fu sion ten sor im ag ing) ir trak tog ra fi ja, ta èiau ðio je sri ty je vis dar trûks ta áro dy mø. Vis dël to, pa ti ki mai pre na ta li nei diag nos ti kai tu rë tø bû ti at lie ka mi ge ne ti niai ty ri mai, ypaè esant di de lei ki to vai ko PCH pa si kar to ji mo ri zi kai [14].…”