Childhood onset hereditary spastic paraplegia

Gene: FBXO31

Green List (high evidence)

Comment on list classification: There are 3 unrelated cases reported in literature with a recurrent de novo heterozygous missense variant in FBXO31, presenting with childhood-onset spasticity, dystonia, ID, with or without cerebral abnormalities on MRI. Hence, this gene can be promoted to Green at the next GMS update, with MOI set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.

Created: 13 Mar 2026, 12:58 p.m. | Last Modified: 13 Mar 2026, 1:04 p.m.

Panel Version: 8.37

PMID: 32989326 Jin et al., 2020
Report of 2 unrelated patients with the same de novo FBXO31 mutation 16:87367889:C:T, p.Asp334Asn. Disease onset was under age two years.
F218-003 - Female, European, presented with spastic diplegia, as well as Esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus.
F699-003 - Male, European, presented with spastic paraplegia, as well as Ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation.

PMID: 33675180 Dzinovic et al., 2021
Report of a 9yo boy of Slovakian descent, with a de novo FBXO31 variant c.1000G>A (p.Asp334Asn) - trio WES. He presented with complex, non‐progressive movement‐disorder syndrome dominated by spasticity and dystonia. Brain MRI showed bilateral occipital and parietal white‐matter volume reduction, irregular white‐matter dysmyelination. Intellectual disability estimated at Moderate severity (no IQ assessment; loss of speech at the age of 1.5 years, receptive language disorder)
Sources: Literature

Created: 13 Mar 2026, 12:55 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 32989326
• 33675180