The Center for Cerebellar Malformations
Pontocerebellar Hypoplasia (PCH)
Pontocerebellar
hypoplasia (PCH)
Conditions described
as pontocerebellar hypoplasia are also known as pontocerebellar atrophies due
to the progressive atrophy of the brain that is observed on serial brain
imaging. The major brain
regions involved include the ventral pons and often the inferior olivary
nuclei, cerebellar vermis, and cerebellar hemispheres. Supratentorial atrophic
changes include enlargement of the ventricles and extra-axial CSF spaces,
widened cerebral sulci, and thinning of white matter and corpus callosum (Zelnik et al., 1996). Clinically, children with PCH have prenatal onset of
neurological abnormalities, and postnatal severe developmental delay, mental
retardation, and often a seemingly neurodegenerative course (Barth, 1993). The progressive MRI changes may be more apparent
than actual clinical regression (Parisi and Dobyns, 2003; Uhl et al., 1998). The
general clinical course shows neonatal hypotonia, poor feeding, growth
retardation, failure to achieve any significant motor or cognitive milestones,
resulting in severe to profound mental retardation, although there may be
exceptions in mild cases (Zelnik et al., 1996). These
conditions need to be differentiated from infantile neuroaxonal dystrophy,
mitochondrial defects, and PEHO (progressive encephalopathy with edema,
hypsarrhythmia, and optic atrophy) syndrome, and CDGs. Although the term ÔÔinfantile
olivopontocerebellar atrophyÕÕ has been applied to this group of disorders,
this leads to confusion with the adult-onset spinocerebellar ataxia conditions
that are also known as OPCA syndromes (Barth, 1993). Like
CVH, the forms of PCH are individually very rare conditions, with less than 20
published cases. At least 3 forms have been defined on clinical and pathologic
features
PCH1
(PCH associated with spinal muscular atrophy)
PCH1 is characterized
by neonatal respiratory insufficiency, often with ventilator dependency and
congenital contractures (arthrogryposis). The clinical course is characterized
by bulbar dysfunction, feeding and respiratory problems, and death generally
within the first year of life (Barth 1993; Barth 2000; Norman 1961;
Rudnik-Schoneborn et al 2003; Chou, 1990 #109). MRI findings include hypoplastic brainstem and cerebellum.
Degeneration of the anterior horn cells of the spinal cord resembles spinal
muscular atrophy (SMA) histologically, and the muscle biopsy shows grouped
atrophy consistent with this pathogenesis. The disease is genetically distinct
from SMA, however, and the genetic causes are unknown.
PCH2 with dyskinesia
In PCH2, the neonatal presentation is of marked microcephaly and absence of normal swallow and feeding ability. The microcephaly is progressive, and generalized epilepsy with marked chorea that has Its onset within the first few months of life and that evolves into dystonia in later childhood (Barth et al., 1995; Barth et al., 1990). Most affected children die within the first decade of life. Imaging reveals atrophy of the ventral pons and cerebellar hemispheres and vermis with progressive subcortical atrophy. Spinal anterior horn cells are normal, differentiating this condition from PCH1. There are several reports of less severe variants, and the suggestion of heterogeneity in PCH2. No genes have been mapped for this autosomal recessive condition.
Other
forms of Pontocerebellar hypoplasia
Several other individual families
with PCH have been described, and show evidence of genetic mapping to distinct
loci, implying that there are several distinct genetic entities. These families display hypoplasia/atrophy
of the cerebellum, with a predilection for the cerebellar vermis, as well as
pontine hypoplasia. Neither
features of spinal muscular atrophy or dyskinesia are prominent. Mental retardation, optic atrophy, and
skin anomalies are often associated (Delague et al., 2001; Delague et
al., 2002; Megarbane et al., 2001; Rajab et al., 2003; Straussberg et al.,
2005).
MRI Scans
Left-axial
cut; Right-.Sagittal cut; Arrows indicate hypoplasia.