Clinical Guidance

The FLNB-related disorders can be divided into two groups of conditions caused by loss of function or gain of function of filamin-B. Biallelic loss-of-function pathogenic variants in FLNB cause spondylocarpotarsal synostosis syndrome (FLNB-SCT). Monoallelic gain-of-function pathogenic variants in FLNB cause a spectrum of phenotypic severity ranging from apparently isolated clubfoot to Larsen syndrome (FLNB-LS), atelosteogenesis type 3 (FLNB-AO3), and atelosteogenesis type 1 (FLNB-AO1), which is perinatal lethal. For the purposes of this GeneReview, the previously described entities Piepkorn dysplasia, boomerang dysplasia, and spondylohumerofemoral (giant cell) dysplasia are subsumed under the FLNB-AO1 spectrum.

Diagnostic Criteria

Formal diagnostic criteria for FLNB-related disorders have not been established. The FLNB-related disorders can be divided into two groups of conditions caused by loss of function or gain of function of filamin-B. Biallelic loss-of-function pathogenic variants in FLNB cause spondylocarpotarsal synostosis syndrome (FLNB-SCT). Monoallelic gain-of-function pathogenic variants in FLNB cause a spectrum of phenotypic severity ranging from apparently isolated clubfoot to Larsen syndrome (FLNB-LS), atelosteogenesis type 3 (FLNB-AO3), and atelosteogenesis type 1 (FLNB-AO1), which is perinatal lethal. For the purposes of this GeneReview, the previously described entities Piepkorn dysplasia and boomerang dysplasia are subsumed under the FLNB-AO1 spectrum.

Management Guidelines

No clinical practice guidelines for FLNB-related disorders have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with an FLNB-related disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. FLNB-Related Disorders: Recommended Surveillance