Table 1 Overview of PCH subtypes with associated gene defect. DSD = Disorders of Sex Development. * Imaging suggests postnatal onset of neurodegeneration in (a subset of) patients in this group
From: What’s new in pontocerebellar hypoplasia? An update on genes and subtypes
Subtype | Symptoms/ distinctive features in addition to PCH | Subcategory and gene (#OMIMnr) | Gene function | Key references |
|---|---|---|---|---|
PCH1 | Motor neuron degeneration, muscle weakness, hypotonia, respiratory insufficiency, congenital contractures | PCH1A: VRK1 (#607596) | Neuronal migration | |
PCH1B: EXOSC3 (#614678) | mRNA degradation | |||
PCH1C: EXOSC8 (#616081) | mRNA degradation | [18] | ||
PCH1D: SLC25A46 (*610826) | Mitochondrial fission and fusion | |||
PCH2 | Generalized clonus, impaired swallowing, Dystonia, chorea, progressive microcephaly | PCH2A: TSEN54 (#277470) | tRNA splicing | |
PCH2B: TSEN2 (#612389) | tRNA splicing | |||
PCH2C: TSEN34 (#612390) | tRNA splicing | [21] | ||
PCH2D*: SEPSECS (#613811) | Selenocysteine synthesis | |||
PCH2E: VPS53 (#615851) | Unknown | [30] | ||
PCH2F: TSEN15 (#617026) | tRNA splicing | [26] | ||
PCH3 | Facial dysmorphism, optic atrophy, cerebellar atrophy | PCLO* (#608027) | Regulation synaptic protein & vesicle formation | |
PCH4 | Severe form of PCH2 with congenital contractures and polyhydramnios | TSEN54 (#225753) | tRNA splicing | |
PCH5 | Severe form of PCH2 with congenital contractures and polyhydramnios (identical to PCH4) | TSEN54 (#610204) | tRNA splicing | |
PCH6 | Hypotonia, seizures, elevated CSF lactate, progressive supratentorial atrophy | RARS2* (#611523) | Arginyl tRNA synthetase | |
PCH7 | DSD, thin corpus callosum, enlarged ventricles | TOE1 (#614969) | RNA processing | [52] |
PCH8 | Abnormal muscle tone, dystonia, ataxia, no/little disease progression. Non-degenerative. | CHMP1A (#614961) | Regulation INK4A | [54] |
PCH9 | Abnormal muscle tone, impaired swallowing, corpus callosum agenesis and ‘Fig. 8’ configuration of brainstem | AMPD2 (#615809) | Regulation GTP synthesis | |
PCH10 | Abnormal muscle tone, seizures, motor neuron degeneration, mild cerebellar hypoplasia/atrophy | CLP1 (#615803) | tRNA splicing | |
PCH11 | Non-progressive/ non-degenerative PCH. | TBC1D23 (# 617695) | Intracellular vesicle transport |