Arthrogryposis

Gene: KIF21A

Green List (high evidence)

Further case described in PMID: 37921537 Bhola et al., 2023.

Created: 24 Feb 2026, 5:20 p.m. | Last Modified: 24 Feb 2026, 5:20 p.m.

Panel Version: 9.23

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
arthrogryposis, MONDO:0008779; fetal akinesia

Publications

• 37921537

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 10 Oct 2023, 4:08 p.m. | Last Modified: 10 Oct 2023, 4:08 p.m.

Panel Version: 5.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on classification: There is sufficient evidence to recommend this gene to NHS GMS for promoting to green rating.

There are two unrelated families with homozygous loss of function variants in KIF21A were reported with severe fetal akinesia with arthrogryposis multiplex in PMID:34740919. Hannah Robinson (South West Genomic Laboratory Hub) reported an additional case identified in Exeter Genomics Laboratory exhibiting homozygous nonsense variant in KIF21A and was diagnosed with arthrogryposis.

In addition, PMID:32686171 reports overlapping phenotypes observed in KIF21A null piglets, where a 63-bp insertion in exon 2 of the porcine KIF21A gene is associated with arthrogryposis multiplex congenita.

Created: 7 Feb 2023, 5:34 p.m. | Last Modified: 7 Feb 2023, 5:34 p.m.

Panel Version: 4.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
arthrogryposis, MONDO:0008779; fetal akinesia

Publications

• 32686171
• 34740919

Green List (high evidence)

Falb et al 2023 (PMID: 34740919) describe two unrelated families in which biallelic loss of function variants segregated with a severe form of fetal akinesia characterised by arthrogryposis multiplex, pulmonary hypoplasia and variable facial dysmorphisms.

Exeter Genomics Laboratory has identified an unrelated third case homozygous for a nonsense variant in KIF21A. The patient had an antenatal diagnosis of talipes, arthrogryposis, polyhydramnios and lack of fetal movements. At birth, all joints displayed fixed flexion deformities, no primitive reflexes, poor muscle bulk and care was re-oriented shortly after birth.

Taken together, three unrelated cases including segregation evidence in the published families provides sufficient evidence for the gene-disease association.
Sources: Literature, NHS GMS

Created: 18 Jan 2023, 8:49 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Arthrogryposis; fetal akinesia

Publications

• 34740919

Variants in this GENE are reported as part of current diagnostic practice