NORD gratefully acknowledges John M. Graham, JR., MD, ScD, Pediatric Consultant in Clinical Genetics and Dysmorphology, Department of Pediatrics, Cedars-Sinai Medical Center, for assistance in the preparation of this report.
SummaryLarsen syndrome is a rare genetic disorder that has been associated with a wide variety of different symptoms. Characteristic findings of the disorder include dislocations of the large joints, skeletal malformations, and distinctive facial and limb features. Additional findings may include abnormal curvature of the spine, clubfoot, short stature, and breathing (respiratory) difficulties. The classic form of Larsen syndrome is caused by mutations of the FLNB gene. The mutation may occur spontaneously or be inherited as an autosomal dominant trait. Introduction FLNB-related disorders are a group of disorders (including autosomal dominant Larsen syndrome) that occur due to mutations of the Filamin B gene (FLNB) gene. This group includes atelosteogenesis types I and III, boomerang dysplasia and spondylocarpotarsal syndrome. These disorders are characterized by skeletal abnormalities affecting the bones of the hands and feet, the bones of the spine (vertebrae), joint dislocations, and distinctive facial features. The specific symptoms and severity of these disorders may vary greatly even among members of the same family. Researchers have identified individuals with multiple joint dislocations and skeletal anomalies whose condition appears to be inherited as an autosomal recessive trait. These individuals often have different radiological findings than those with classic Larsen syndrome. Mutations in the carbohydrate sulfotransferase 3 (CHST3) gene have been identified in patients with so-called autosomal recessive Larsen syndrome that also includes humero-spinal dysostosis and spondyloepiphyseal dysplasia Omani type. A variant of Larsen syndrome was reported in patients from Reunion Island in the southern Indian Ocean and characterized by dwarfism, hyperlaxity, multiple dislocations and distinctive facial features. It is inherited in an autosomal recessive fashion and results from a founder homozygous missense mutation in B4GALT7. Since these disorders are known to be caused by different genes than classic, autosomal dominant Larsen syndrome, the term autosomal recessive Larsen syndrome should probably be avoided to prevent confusion with clinical disorders resulting from mutations in FLNB.
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