Arthrogryposis

Gene: FGFR3

Green List (high evidence)

Comment on phenotypes: OMIM phenotype accessed 20th Jan 2026.

Created: 20 Jan 2026, 3:35 p.m. | Last Modified: 20 Jan 2026, 3:35 p.m.

Panel Version: 9.18

Comment on mode of inheritance: Mutations in FGFR3 may rarely cause Camptodactyly-Tall Stature-Scoliosis-Hearing Loss (CATSHL) syndrome. To date, 3 families with dominant and 1 with recessive CATSHL syndrome have been reported. All dominant cases involve a missense change at the same residue (621), while recessive disease was cause by a missense variant p.Thr546Lys. The mode of inheritance for FGFR3 should be changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted for Arthrogryposis, until more cases emerge in support of recessive inheritance.

Created: 20 Jan 2026, 3:34 p.m. | Last Modified: 20 Jan 2026, 3:34 p.m.

Panel Version: 9.15

CATSHL syndrome cases:
PMID: 37990933 Cannova et al., 2024
Report of a 12-year-old Italian girl and her father, both had marked postnatal tall stature, camptodactyly and clinodactyly, scoliosis and juvenile-onset hearing loss - diagnosed with CATSHL syndrome, both heterozygous for c.1861C>T (p.Arg621Cys) in FGFR3.

PMID: 27139183 Escobar et al., 2016
16yo female proband, with family history of dominant CATSHL syndrome, heterozygous for (FGFR3):c.1862G>A (p.Arg621His). Phenotype: finger contractures, progressive sensorineural hearing loss, scoliosis, leg length discrepancy. Normal intellect and development.

PMID: 24864036 Makrythanasis et al., 2014
2 male sibs with CATSHL syndrome - severe skeletal deformities, tall stature and hearing impairment, mild ID in proband (IQ 70). Both harboured a homozygous FGFR3 missense variant NM_000142.4:c.1637C>A: p.(Thr546Lys). Parents and unaffected sister were het carriers.

PMID: 17033969 Toydemir et al., 2006
Large Utah pedigree with 27 living affected family members with CATSHL syndrome - autosomal dominant inheritance, variant FGFR3:c.1862G>A, p.(Arg621His) segregated with disease. Camptodactyly of the hands and/or feet was present in 18/20 assessed individuals

Created: 20 Jan 2026, 3:28 p.m. | Last Modified: 20 Jan 2026, 3:28 p.m.

Panel Version: 9.15

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
CATSHL syndrome, OMIM:610474

Publications

• 17033969
• 24864036
• 27139183
• 37990933

Green List (high evidence)

Only identified in two families but one with 20 affected members segregating the same mutations. Recognised on G2P. Supported by mouse model

Created: 5 Jan 2017, 2:53 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
CATSHL syndrome 610474

Publications

• 17033969