Childhood onset hereditary spastic paraplegia

Gene: ATAD3A

PMID: 34387651 - one patient with spastic diplegic gait that appeared stable since early infancy, harbouring the same p.(Gly355Asp) variant in ATAD3A as seen in the patient previously reported by Cooper et al. 2017 (PMID: 28158749). This is the second case where the early phenotype was notable for spasticity in early childhood and therefore upgrading the rating from Red to Amber.

Created: 18 Apr 2023, 10:23 a.m. | Last Modified: 18 Apr 2023, 10:23 a.m.

Panel Version: 4.4

Gene was reassessed following a Green review by Zornitza Stark. To date, ATAD3A has only been linked to spastic paraplegia in one family with a heterozygous variant (PMID: 28158749). Spasticity has been reported in 6/15 individuals with Harel-Yoon syndrome (MIM# 617183) associated with monoallelic and biallelic SNVs in this gene (PMID: 27640307; 32607449; 32933822; 33845882). However, the core phenotype is characterised by other features for which cases are more likely to get recognised, including psychomotor delay, hypotonia, cerebellar atrophy, neuropathy, hypertrophic cardiomyopathy, and ophthalmologic abnormalities. The HSP family did not share several of these features, indicating this is a distinct phenotype. As there is only one family with HSP, maintaining Red rating until further evidence emerges.

Created: 6 Jul 2021, 10:51 a.m. | Last Modified: 6 Jul 2021, 10:51 a.m.

Panel Version: 2.44

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Harel-Yoon syndrome, OMIM:617183; Spastic paraplegia

Publications

• 28158749
• 27640307
• 33845882
• 34387651

Green List (high evidence)

Five unrelated families with recurrent de novo missense, p.Arg528Trp with syndromic neurodevelopmental disorder characterised by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy. In addition, mother and child reported in PMID 28158749 with HSP and axonal neuropathy of childhood onset.

Created: 17 Sep 2020, 10:19 a.m. | Last Modified: 17 Sep 2020, 10:19 a.m.

Panel Version: 2.15

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Harel-Yoon syndrome, MIM# 617183

Publications

• 28158749
• 27640307

Red List (low evidence)

Added as a Red gene based on the available literature. There is only one case. PMID: 28158749 describes a family with monoallelic variant (c.1064 G>A, G355D) where affected mother and son do not have optic atrophy nor HCM but have hereditary spastic paraplegia.
Sources: Literature

Created: 24 Aug 2020, 3:18 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Harel-Yoon syndrome, 617183

Publications

• 28158749