Multiple joint dislocations and laxity

Gene: FLNB

Green List (high evidence)

Well-established gene-disease association. FLNB spectrum of phenotypes ranging from mild spondylocarpotarsal synostosis (SCT) syndrome and Larsen syndrome (LS) to the more severe phenotypic continuum of atelosteogenesis types I (AOI, includes Boomerang dysplasia) and III (AOIII) and Piepkorn osteochondrodysplasia (POCD).

SCT AR - PMID: 14991055, 17360453, 20301736, 29566257 - caused by biallelic loss of function/null (frameshift/nonsense) variants.

Osteochondrodysplasias (LS, AOI, AOIII, POCD) AD - PMID: 14991055, 16801345, 20301736, 22190451 - caused by monoallelic missense/in-frame indel variants. Commonly de novo variant, particularly in the lethal more severe forms of disease. Variable phenotypes reported for some recurrent variants. Variants cluster actin-binding domain (ABD) and filamin repeats 13-17. The mechanism of disease for variants in the ABD is gain of function leading to protein aggregation, whereas variants in the filamin repeats are expected to have a different mechanism of disease.

Created: 11 May 2022, 2:27 a.m. | Last Modified: 11 May 2022, 2:27 a.m.

Panel Version: 0.14081

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
spondylocarpotarsal synostosis syndrome MONDO:0010094; filamin-related bone disorder MONDO:0019690

Publications

• 14991055
• 17360453
• 20301736
• 29566257
• 16801345
• 22190451