Skeletal dysplasia

Gene: FGFR3

Green List (high evidence)

Comment on mode of inheritance: FGFR3 variants are associated with several dominant conditions that include skeletal dysplasia. However, evidence of recessive inheritance is lacking. To date, one family has been reported with autosomal recessive Camptodactyly-Tall Stature-Scoliosis-Hearing Loss (CATSHL) syndrome. 3 other families were reported with a dominantly inherited CATSHL syndrome. 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 Skeletal dysplasia, until more cases emerge in support of recessive inheritance.

Created: 20 Jan 2026, 3:41 p.m. | Last Modified: 20 Jan 2026, 3:41 p.m.

Panel Version: 8.30

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, 3:37 p.m. | Last Modified: 20 Jan 2026, 3:37 p.m.

Panel Version: 8.30

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
CATSHL syndrome, OMIM:610474; camptodactyly-tall stature-scoliosis-hearing loss syndrome, MONDO:0012504

Publications

• 17033969
• 24864036
• 27139183
• 37990933

Green List (high evidence)

This gene should definitely be green

Created: 18 Apr 2019, 1:51 p.m.

FGFR3 chondrodysplasia group, craniosynostosis syndromes gp of SD, polydactyly-syndactyly-triphalangism SD gp. Truncating/fs variants have not been reported in skeletal phenotypes though mutation of the stop codon has been.; Review on behalf of Tracy Lester

Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Achondroplasia 100800; CATSHL syndrome 610474; Crouzon syndrome with acanthosis nigricans 612247; Hypochondroplasia 146000; LADD syndrome 149730; Muenke syndrome 602849; SADDAN 616482; Thanatophoric dysplasia, type I 187600; Thanatophoric dysplasia, type II 187601

Mode of pathogenicity
Other - please provide details in the comments

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

I don't know

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: FGFR3; Initial rating suggestion: NONE GIVEN, so given Amber rating when first uploading reviews from Tracy Lester.

Created: 6 Mar 2019, 11:36 a.m.

Green List (high evidence)

Listed as associated with Skeletal Dysplasia by Gene Advisor (June 2016), Steve Abbs

Created: 27 Jul 2016, 9:35 a.m.

Comment when marking as ready: Associated with phenotypes in G2P. Numerous variants reported in these phenotypes.

Created: 12 Jul 2016, 7:19 a.m.

Green List (high evidence)

Tier 1

Created: 17 Jun 2016, 8:04 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Achondroplasia 100800; CATSHL syndrome 610474; Crouzon syndrome with acanthosis nigricans 612247; Hypochondroplasia 146000; LADD syndrome 149730; Muenke syndrome 602849; SADDAN 616482; Thanatophoric dysplasia, type I 187600; Thanatophoric dysplasia, type II 187601

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