Arthrogryposis

Gene: AGRN

Comment on list classification: Upgrading from Red to Amber as two families have now been identified with FADS which presents with multiple joint contractures (PMID: 31730230; 39807604)

Created: 29 Aug 2025, 11:32 a.m. | Last Modified: 29 Aug 2025, 11:32 a.m.

Panel Version: 9.7

PMID: 39807604 (2025) - biallelic null variants in AGRN leading to a fetal akinesia deformation sequence (FADS) identified in a second family affecting three pregnancies. WES revealed a maternally inherited heterozygous variant c.952+1_952+3del and split-read analysis identified a paternally inherited heterozygous 41.33 kb deletion, encompassing exons 1 and 2 of AGRN.

Created: 29 Aug 2025, 11:29 a.m. | Last Modified: 29 Aug 2025, 11:29 a.m.

Panel Version: 9.4

Copied from review by Rhiannon Mellis (GOSH) on the Fetal anomalies panel, 30 Sep 2020:

Geremek et al. 2019 (PMID: 31730230): First case report associating AGRN with lethal fetal phenotype (FADS) (including contractures of fingers and all four limbs) - unlike previous reported postnatal cases, the fetus had null variants on both alleles (a frameshift in trans with a 148kb deletion), which the authors suggest as a possible explanation for the severe phenotype.

Created: 21 Jan 2021, 1:28 p.m. | Last Modified: 21 Jan 2021, 1:28 p.m.

Panel Version: 3.51

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fetal akinesia deformation sequence, MONDO:0008824

Publications

• 31730230
• 39807604

Red List (low evidence)

Not congenital-no arthrogryposis

Created: 4 Jan 2017, 1:39 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects 615120