Childhood onset hereditary spastic paraplegia

Gene: NFU1

Green List (high evidence)

Comment on list classification: There are patients from at least nine unrelated families reported with childhood-onset hereditary spastic paraplegia and with biallelic NFU1 variants. Hence, this gene should be promoted to green rating in the next GMS update.

Created: 14 Apr 2026, 4:43 p.m. | Last Modified: 14 Apr 2026, 4:43 p.m.

Panel Version: 8.48

PMID:36256512 (2022) reported 19 affected individuals from 10 independent families with nine different biallelic NFU1 missense variants. They are associated with a spectrum of early-onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Gait acquisition was delayed due to either the insidious onset of limb spasticity in 13/19 individuals or spasticity precipitated by a deterioration in the context of a febrile illness in 4/19 individuals (Fig. 1B). The lower limb spasticity was detected at a mean age of 12 ± 6 months in the cohort. Spasticity was progressive leading to contractures in 13/19 persons and necessitating Achilles' tendon repair surgery in 4/19 affected individuals.

This gene has been associated with relevant phenotype in OMIM (MIM #620938), which was last accessed on 14 April 2026.
Sources: Literature

Created: 14 Apr 2026, 4:38 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 93, autosomal recessive, OMIM:620938; spastic paraplegia 93, autosomal recessive, MONDO:0975796

Publications

• 36256512