Multiple joint dislocations and laxity
Gene: FLNB
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
Source Victorian Clinical Genetics Services was added to FLNB. Added phenotypes Atelosteogenesis, type I 108720; Atelosteogenesis, type III 108721; Larsen syndrome 150250; Spondylocarpotarsal synostosis syndrome 272460; Boomerang dysplasia 112310 for gene: FLNB
gene: FLNB was added gene: FLNB was added to Multiple joint dislocations and laxity. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: FLNB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: FLNB were set to Boomerang dysplasia 112310; Atelosteogenesis, type I 108720; Atelosteogenesis, type III 108721; Larsen syndrome 150250; Spondylocarpotarsal synostosis syndrome 272460