Table 2.
Differential diagnosis of Pontocerebellar Hypoplasia (PCH)
| Disease | Distinctive features | Gene(s) involved | references |
|---|---|---|---|
| Congenital disorder of Glycosylation Ia (CDGIa) | Clinical: neonatal onset multi organ failure, dysmorphic features, ataxia. Microcephaly. MRI: global PCH with superimposed atrophy, supratentorial atrophy, ventriculomegaly, delayed myelinisation. |
PMM2 | [68, 69, 72] |
| CASK- related disorders | Clinical: facial dysmorphism, sensorineural hearing loss, ophthalmologic abnormalities. Developmental progress in a subgroup of patients. No MND or chorea. Progressive microcephaly. MRI: variable degree of PCH, equally affecting hemispheres and vermis. Cortical malformations can be present. |
CASK | [73-76] |
| Tubulin defects | Clinical: DD, seizures. Progressive microcephaly. Optic atrophy in some cases. MRI: cortical malformations (eg lissencephaly, polymicrogyria) with cerebellar hypoplasia and brainstem malformations. |
TUBA1A, TUBB2B, TUBB3, TUBB5, TUBA8 | [77-79] |
| RELN & VLDLR mutations | Clinical: Severe DD, hypotonia, epilepsy, nystagmus. In VLDLR: non-progressive ataxia, quadrupedal gait. MRI: lissencephaly, severe PCH and abnormal hippocampus, milder in VLDLR. |
RELN, VLDLR | [80-82] |
| α- dystroglycan related dystrophies (WWS, MEB, Fukuyama congenital muscular dystrophy) | Clinical: severe DD, muscle weakness with increased CK, ophthalmologic abnormalities. WWS at the severest end of the spectrum. MRI: wide spectrum of brain malformations including cobblestone lissencephaly, PCH, congenital hydrocephalus. |
POMT1, POMT2, POMGnT1, LARGE, FKTN, FKRP, ISPD, FKR, FKRP | [83, 84, 85] |
| X-linked Hoyeraal-Hreidarsson syndrome | Clinical: IUGR, microcephaly, failure to thrive, progressive bone marrow failure, aplastic anemia, combined immunodeficiency, some symptoms of DC. MRI: PCH, delayed myelinisation, focal high intensities in brainstem and thalamus, subcortical calcifications. |
DKC1 | [86-87] |
| Pediatric onset Spinocerebellar Ataxia | Clinical: Ataxia, developmental progress, some cases with retinitis pigmentosa or cone-rod dystrophy. MRI: (ponto) cerebellar hypoplasia/atrophy, no supratentorial atrophy. |
ITPR1, ATXN7, ATXN2 | [88-92] |
| Extreme prematurity (< 32 weeks) | Clinical: motor and cognitive impairment of variable degree, autism spectrum disorders MRI: PCH, signs of cerebellar or cerebral injury, eg hemorrhage. Non progressive. |
n/a | [95-97] |
MND motor neuron degeneration, DD developmental delay, CK creatine kinase, WWS Walker-Warburg syndrome, MEB Musce Eye Brain disease, IUGR Intrauterine Growth Retardation, DC dyskeratosis congenita