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    Spondylocarpotarsal Synostosis Syndrome

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    Submitted by: Bruce Ren
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    Spondylocarpotarsal synostosis syndrome is a disorder that affects the development of bones throughout the body. Newborns with this disorder are of approximately normal length, but impaired growth of the torso results in short stature over time. The bones of the spine (vertebrae) are misshapen and abnormally joined together (fused). The vertebral abnormalities may result in an abnormally curved lower back (lordosis) and a spine that curves to the side (scoliosis).

     

    1. Introduction

    People with spondylocarpotarsal synostosis syndrome have abnormalities and fusion of the bones of the wrist (carpal bones) and ankle (tarsal bones). They may also have inward- and upward-turning feet (clubfeet). Characteristic facial features include a round face, a large forehead (frontal bossing), and nostrils that open to the front rather than downward (anteverted nares).

    Some people with spondylocarpotarsal synostosis syndrome have an opening in the roof of the mouth (a cleft palate), hearing loss, thin tooth enamel, flat feet, or an unusually large range of joint movement (hypermobility). Individuals with this disorder can survive into adulthood. Intelligence is generally unaffected, although mild developmental delay has been reported in some affected individuals.

    2. Frequency

    Spondylocarpotarsal synostosis syndrome is a rare disorder; its prevalence is unknown. At least 25 affected individuals have been identified.

    3. Causes

    Mutations in the FLNB gene cause spondylocarpotarsal synostosis syndrome. The FLNB gene provides instructions for making a protein called filamin B. This protein helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin B attaches (binds) to another protein called actin and helps the actin to form the branching network of filaments that makes up the cytoskeleton. It also links actin to many other proteins to perform various functions within the cell, including the cell signaling that helps determine how the cytoskeleton will change as tissues grow and take shape during development.

    Filamin B is especially important in the development of the skeleton before birth. It is active (expressed) in the cell membranes of cartilage-forming cells (chondrocytes). Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone (a process called ossification), except for the cartilage that continues to cover and protect the ends of bones and is present in the nose, airways (trachea and bronchi), and external ears. Filamin B appears to be important for normal cell growth and division (proliferation) and maturation (differentiation) of chondrocytes and for the ossification of cartilage.

    FLNB gene mutations that cause spondylocarpotarsal synostosis syndrome result in the production of an abnormally short filamin B protein that is unstable and breaks down rapidly. Loss of the filamin B protein appears to result in out-of-place (ectopic) ossification, resulting in fusion of the bones in the spine, wrists, and ankles and other signs and symptoms of spondylocarpotarsal synostosis syndrome.

    A few individuals who have been diagnosed with spondylocarpotarsal synostosis syndrome do not have mutations in the FLNB gene. Researchers are working to identify and confirm additional genetic changes that can cause this disorder.

    3.1 Learn more about the genes associated with Spondylocarpotarsal synostosis syndrome

    4. Inheritance

    Spondylocarpotarsal synostosis syndrome caused by FLNB gene mutations is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

    In a few individuals with signs and symptoms similar to those of spondylocarpotarsal synostosis syndrome but without FLNB gene mutations, the condition appears to have been inherited in an autosomal dominant pattern. Autosomal dominant means one copy of the altered gene in each cell is sufficient to cause the disorder.

    5. Other Names for This Condition

    • congenital scoliosis with unilateral unsegmented bar
    • congenital synspondylism
    • SCT
    • SCT syndrome
    • spondylocarpotarsal syndrome
    • vertebral fusion with carpal coalition

    The entry is from https://medlineplus.gov/genetics/condition/spondylocarpotarsal-synostosis-syndrome

    References

    1. Carapito R, Goldenberg A, Paul N, Pichot A, David A, Hamel A, Dumant-Forest C,Leroux J, Ory B, Isidor B, Bahram S. Protein-altering MYH3 variants areassociated with a spectrum of phenotypes extending to spondylocarpotarsalsynostosis syndrome. Eur J Hum Genet. 2016 Dec;24(12):1746-1751. doi:10.1038/ejhg.2016.84.
    2. Isidor B, Cormier-Daire V, Le Merrer M, Lefrancois T, Hamel A, Le Caignec C,David A, Jacquemont S. Autosomal dominant spondylocarpotarsal synostosissyndrome: phenotypic homogeneity and genetic heterogeneity. Am J Med Genet A.2008 Jun 15;146A(12):1593-7. doi: 10.1002/ajmg.a.32217.
    3. Krakow D, Robertson SP, King LM, Morgan T, Sebald ET, Bertolotto C,Wachsmann-Hogiu S, Acuna D, Shapiro SS, Takafuta T, Aftimos S, Kim CA, Firth H,Steiner CE, Cormier-Daire V, Superti-Furga A, Bonafe L, Graham JM Jr, Grix A,Bacino CA, Allanson J, Bialer MG, Lachman RS, Rimoin DL, Cohn DH. Mutations inthe gene encoding filamin B disrupt vertebral segmentation, joint formation andskeletogenesis. Nat Genet. 2004 Apr;36(4):405-10.
    4. Sawyer GM, Clark AR, Robertson SP, Sutherland-Smith AJ. Disease-associatedsubstitutions in the filamin B actin binding domain confer enhanced actin bindingaffinity in the absence of major structural disturbance: Insights from thecrystal structures of filamin B actin binding domains. J Mol Biol. 2009 Jul31;390(5):1030-47. doi: 10.1016/j.jmb.2009.06.009.
    5. Yang CF, Wang CH, Siong H'ng W, Chang CP, Lin WD, Chen YT, Wu JY, Tsai FJ.Filamin B Loss-of-Function Mutation in Dimerization Domain CausesAutosomal-Recessive Spondylocarpotarsal Synostosis Syndrome with Rib Anomalies.Hum Mutat. 2017 May;38(5):540-547. doi: 10.1002/humu.23186.
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