Gene(s) | Phenotype/Disorder | MOI | Brain MRI Findings | Clinical Characteristics |
|---|
B3GALNT2B4GAT1DAG1FKRPFKTNGMPPBISPDLARGE1POMGNT1POMGNT2POMKPOMT1POMT2RXYLT11 | Alpha-dystroglycanopathies | AR | Wide spectrum of brain malformations incl cobblestone lissencephaly hydrocephalus | Muscle weakness ophthalmologic abnormalities |
CASK | ID microcephaly w/pontine cerebellar hypoplasia (See CASK Disorders.) | XL | Neocortical dysplasia (simplified gyral pattern, thin brain stem w/flattening of the pons) severe cerebellar hypoplasia (pontocerebellar hypoplasia) | Heterozygous females have severe or profound ID structural brain anomalies incl mild congenital microcephaly severe postnatal microcephaly.; Hemizygous males are more severely affected. |
CHMP1A | PCH82 | AR | MRI findings similar to those of PCH2 | Microcephaly, delayed walking, variable foot deformities, chorea, dystonic posturing, impaired cognition EXOSC3 EXOSC8 SLC25A46 |
VRK1 | PCH12,3 (See EXOSC3-PCH.) | AR | Pontine atrophy may not be present in some individuals. | Lower motor neuron deficits due to loss of anterior horn cells; manifestations of peripheral denervation incl weakness muscle hypotonia from birth; Mixed central (spastic, dystonic) peripheral pareses may be present in those w/prolonged survival; some children w/PCH1 die at an early age.4 |
40 genes (e.g., PMM25) | Congenital disorders of glycosylation (CDG); see also PMM2-CDG (CDG-Ia). | AR(XL) | Pontocerebellar hypoplasia w/superimposed atrophy, delayed myelination | Dysmorphic features, ataxia, organ failure in neonatal period |
PCLO | PCH32 | AR | — | — |
RARS2 | PCH62 | AR | Very rare; CSF lactate concentration | — |
RELN | Lissencephaly 2 (OMIM 257320) | AR | Classic lissencephaly w/coexistent cerebellar pontine hypoplasia | — |
SEPSECS | PCH22 | AR | Progressive cerebello-cerebral atrophy closely resembles mild PCH2. | Clinical findings closely resemble mild PCH2. |
TOE1 | PCH72 | AR | PCH | Disorders of sex development VLDLR |
VLDLR cerebellar hypoplasia | AR | Gross cerebellar hypoplasia, a flat ventral pons, simplified gyri | Ataxia ID AR = autosomal recessive; ID = intellectual disability; MOI = mode of inheritance; PCH = pontocerebellar hypoplasia; XL = X-linked 1. OMIM Phenotypic Series: Muscular dystrophy-dystroglycanopathy, type A 2. 3. | — |
