Table 1 PCH subtypes.

PCH1

Neonatal period: Hypotonia, impaired swallowing, congenital contractures and/or polyhydramnios, primary hypoventilation, progressive microcephaly.

MRI: Pontocerebellar hypoplasia.

Cerebellar hypoplasia: hemispheres > > vermis, areas of stunted or absent folial development. Cerebellar dentate nucleus present as tiny remnants.

Olivary nucleus: absent folding and gliosis.

Pons: loss of ventral nuclei and transverse fibers.

Spinal cord: Anterior horn cell degeneration.

Peripheral nerves and muscle: chronic denervation.

One family with the common TSEN54 mutation.

One case with missense plus splice site mutations in RARS2.

One atypical mild family with nonsense mutations in VRK1.

Locus unknown in the majority.

[6, 7, 10, 20, 21, 40, 42]

PCH2

Neonatal period: Clonus, impaired swallowing.

Infancy and later: Chorea, variable spastic pareses; progressive microcephaly. Severe impairment of cognitive and motor development.

MRI: Variable neocortical atrophy, pontocerebellar hypoplasia.

Cerebellar hypoplasia: hemispheres > > vermis. Segmental degeneration of cerebellar cortex. Fragmentation of cerebellar dentate nucleus.

Olivary nucleus: neuron loss and decreased folding.

Pons: progressive loss of ventral nuclei and transverse fibers.

Cerebral cortex: progressive atrophy

TSEN54: p.A307S, A307S most common in 75 families.

Rarely: Other TSEN54 missense mutations in 3 families, TSEN2 mutations in 2 families, TSEN34 mutations in 1 family.

[15, 18–20, 28, 37]

PCH3

Neonatal period: Hypotonia, impaired swallowing.

Infancy and later: Short stature progressive microcephaly, optic atrophy.

MRI: Neocortical and cerebellar atrophy, pontocerebellar hypoplasia; Pons and cerebellum equally affected.

No autopsies performed.

Locus on chromosome 7 q in 2 families.

[30–32]

PCH4

Neonatal period: Hypertonia, severe clonus, polyhydramnios and/or contractures; primary hypoventilation.

MRI: Delayed neocortical maturation, pontocerebellar hypoplasia; microcephaly on autopsy.

Cerebellar hypoplasia: hemispheres > > vermis, areas of stunted or absent folial development. Cerebellar dentate nucleus present as tiny remnants

Olivary nucleus: absent folding and gliosis.

Pons: loss of ventral nuclei and transverse fibers.

TSEN54: Compound heterozygosity for p.A307S plus nonsense or splice site mutations in 10 families. Three missense mutations in 1 family.

[14, 16, 19, 20, 37]

PCH5

Prenatal/neonatal period: Clonus or seizures.

Neonatal period: Persistent clonus, microcephaly and pontocerebellar hypoplasia on autopsy.

Cerebellar hypoplasia: cortical involvement as in PCH4, but vermal cortex more extensively affected than hemispheric cortex; subtotal loss of cerebellar dentate nucleus.

Olivary nucleus: absent folding.

Pons: loss of ventral nuclei and transverse fibers.

TSEN54: Compound heterozygosity for p.A307S plus splice site mutation in 1 family.

[11, 20]

PCH6

Neonatal period: Hypotonia, clonus, impaired swallowing.

Infancy and later: Progressive microcephaly, spasticity, elevated CSF lactate, edema of extremities.

MRI: Neocortical and cerebellar atrophy, pontocerebellar hypoplasia; Pons and cerebellum equally affected.

No autopsies performed.

Missense and splice site mutations in RARS2 in 2 families.

[12, 39]

PCH7

Neonatal period: No palpable gonads with a micropenis. Hypotonia.

Infancy and later: Regression of penis. Progressive microcephaly, seizures, respiratory distress, poor feeding.

MRI: Pontocerebellar hypoplasia.

Cerebellar hypoplasia: absence of cerebellar hemispheres with neuronal loss.

Olivary nucleus: absent.

Pons: loss of ventral nuclei and transverse fibers.

Cerebral cortex: progressive atrophy.

No locus.

[13]