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Table 2 Differential diagnosis of Pontocerebellar Hypoplasia (PCH)

From: What’s new in pontocerebellar hypoplasia? An update on genes and subtypes

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]

  1. 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