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SUPPLEMENTARY TABLE 1: Features of the Pontocerebellar Hypoplasias
Type
PCH1
 PCH1A
Phenotype
Neuropathology
SC: motor neuron degeneration
Locus
Gene
Ref
Microcephaly; poor sucking;
progressive weakness from anterior
horn disease
Skeletal muscle neurogenic atrophy
14q32.2
VRK1
(1)
EXOSC3
(2, 3)
MRI: small vermis & large cisterna
magna
 PCH1B
Neonatal hypotonia, oculomotor
apraxia, progressive muscle
wasting, progressive microcephaly
CB: profound atrophy, dysmorphic PN, GN 9p13.2
loss; loss of anterior horn motor neurons
MRI: CB atrophy with prominent
sulci and decreased folia volume
PCH2
Progressive microcephaly;
CB: segmental lesions, loss PN & GN; DN:
extrapyramidal dyskinesia & chorea; broken into islands; ION: reduced folding,
hypotonia & hyperreflexia; seizures segmental lesions; ventral pons: neuron
loss; NC: gliotic, otherwise unremarkable;
WM: diffuse gliosis, some cavitation in CB
(4, 5)
 PCH2A
See above
CB: stunted folia with few or no branches,
loss of cortex between folia; ION: partial
undulation
17q25.1
TSEN54
(5)
 PCH2B
Visual impairment; see above
See above
3p25.2
TSEN2
(5)
 PCH2C
Visual impairment; see above
See above
19q13.42 TSEN34
(5)
N/A
4p15.2
SEPSECS
(6, 7)
N/A
7q11q21
N/A
(8)
MRI: hypoplastic CB vermis &
hemisphere; vPons flat
 PCH2D
Profound mental retardation,
progressive microcephaly, severe
spasticity, seizures
MRI: progressive CB atrophy then
cerebral atrophy
PCH3
Neonatal hypotonia and
hyperreflexia; microcephalybrachycephaly; seizures; optic
atrophy & prominent eyes
MRI: small brainstem & vermis; CB
& cerebral atrophy
PCH4
Neonatal encephalopathy;
microcephaly; myoclonus;
hypertonia & joint contractures;
central respiratory failure
Micrencephaly; CB: partial preservation in
flocculus & nodulus, severe depletion &
gliosis of hemispheres; DN: broken into
small islands; severe brainstem
hypoplasia; ION: unfolded and missing
segments; vPons: extensive neuron loss;
diffuse white matter gliosis; neocortex
unremarkable
17q25.1
TSEN54
(4, 5, 9,
10)
PCH5
Seizures
Cerebellum and brainstem loss; vermis
more involved than hemispheres; ION:
dysplastic; DN: immature
17q25.1
TSEN54
(11, 12)
PCH6
Hypotonia, apnea, poor sucking;
seizures; later microcephaly
(This report)
6q15
RARS2
(13, 14)
CB hemispheres, vPons, & ION absent;
NC: atrophy, absent projection fibres;
denuded ependyma and subependymal
gliosis;
N/A
N/A
(15)
N/A
16q24.3
CHMP1A
(16)
MRI: CB, pons, cerebral cortical
hypoplasia and progressive atrophy
Lab: respiratory chain defects
PCH7
Hypotonia, microcephaly, apneic
episodes, seizures; micropenis &
ambiguous genitalia
MRI: pontocerebellar hypoplasia,
enlarged ventricles, reduced
periventricular white matter
PCH8
MRI: severe reduction in cerebellar
vermis & hemispheres, with
preservation of folia; small pons,
and cerebral cortex; microcephaly
Abbreviations: CHMP1A: chromatin-modifying protein 1A; EXOSC3: exosome component 3; RARS2: arginyl-tRNA synthetase 2
(mitochondrial form); SEPSECS: O-phosphoserine tRNA-selenocysteine tRNA synthase; TSEN: tRNA splicing endonuclease (types: 2,
34, 54); VRK1: vaccinia-related kinase 1; CB: cerebellum or cerebellar; DN: dentate nucleus; GN: granular neurons; ION: inferior
olivary nucleus; NC: neocortex; PN: Purkinje neurons; vPons: ventral pons; WM: white matter
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