Cerebellar hypoplasia

Gene: CDK5

Green List (high evidence)

Comment on list classification: Upgrading from Red to Green - 2 unrelated families with the same severe phenotype comprising lissencephaly and supportive animal models.

Created: 23 Sep 2025, 4:19 p.m. | Last Modified: 23 Sep 2025, 4:19 p.m.

Panel Version: 1.79

- PMID: 25560765 (2015) - Homozygous splice site variant g.IVS8+1G>A p.V162SfsX19 segregated with a lethal form of lissencephaly with cerebellar hypoplasia in 4 patients and 25 healthy relatives from one consanguineous family. Affected newborns had dysmorphic facial features, HC in normal-low range, lymphedema, arthrogryposis multiplex, and intractable seizures. Functional studies of the variant showed loss-of-function of the gene product.

- PMID: 40186457 (2025) - Homozygous missense variant c.149G>A (p.Arg50Gln) in an infant with diffuse agyria, cerebellar hypoplasia, agenesis of the corpus callosum, refractory seizures, pyramidal signs, microcephaly, and growth failure. The disease course and severity were similar to those observed in the patients in the first report. Functional studies support deleterious effect of the variant.

Animal models:
Brains of Cdk5-null mice lacked cortical laminar structure and cerebellar foliation (PMID: 8855328). Cdk5 knockout in the ferret cerebral cortex also markedly impaired cortical folding (PMID: 28854363).

Created: 23 Sep 2025, 4:18 p.m. | Last Modified: 23 Sep 2025, 4:18 p.m.

Panel Version: 1.78

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Lissencephaly 7 with cerebellar hypoplasia, OMIM:616342

Publications

• 25560765
• 40186457
• 28854363
• 8855328

Only reported in one family -4 affected relatives. Supported by evidence from mouse model

Created: 14 Nov 2016, 2:32 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Lissencephaly 7 with cerebellar hypoplasia 616342

Publications

• 25560765, 15067135