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Gene: NKX6-2

Green List (high evidence)

Spastic ataxia-8 with hypomyelinating leukodystrophy is an autosomal recessive progressive neurodegenerative disorder characterized by onset of primarily motor dysfunction within the first year of life.

At the severe end of the spectrum is neonatal-onset nystagmus, severe spastic tetraplegia with joint contractures and scoliosis, and visual and hearing impairment, all of which rapidly progress resulting in death in early childhood. Biallelic pathogenic variants in the homeobox domain (c.487C>G, c.606delinsTA, c.565G>T, c.599G>A, c.589C>T, c.608G>A, c.196delC) are associated with a severe early onset phenotype (GeneReviews PMID: 30285346).

At the milder end of the spectrum is normal achievement of early motor milestones in the first year of life followed by slowly progressive complex spastic ataxia with pyramidal and cerebellar findings with loss of developmental milestones (GeneReviews PMID: 30285346).

Created: 14 Jan 2025, 11:06 p.m. | Last Modified: 14 Jan 2025, 11:06 p.m.

Panel Version: 1.992

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy MIM#617560

Publications

• 28575651
• 15601927
• 32246862
• 32004679
• 30285346