Larsen syndrome (LS) is a congenital disorder discovered in 1950 by Larsen and associates when they observed dislocation of the large joints and face anomalies in six of their patients. Patients with Larsen syndrome normally present with a variety of symptoms, including congenital anterior dislocation of the knees, dislocation of the hips and elbows, flattened facial appearance, prominent foreheads, and depressed nasal bridges. Larsen syndrome can also cause a variety of cardiovascular and orthopedic abnormalities. This rare disorder is caused by a genetic defect in the gene encoding filamin B, a cytoplasmic protein that is important in regulating the structure and activity of the cytoskeleton. The gene that influences the emergence of Larsen syndrome is found in chromosome region, 3p21.1-14.1, a region containing human type VII collagen gene. Larsen syndrome has recently been described as a mesenchyme disorder that affects the connective tissue of an individual. Autosomal dominant and recessive forms of the disorder have been reported, although most cases are autosomal dominant. Reports have found that in Western societies, Larsen syndrome can be found in one in every 100,000 births, but this is most likely an underestimate because the disorder is frequently unrecognized or misdiagnosed. Signs and symptoms
Common symptoms
Symptoms are related to defects in connective tissue. Congenital anterior dislocation of the knees
Dislocation of hips and shoulders
Flattened facial appearance
Prominent forehead
Depressed nasal bridge
Club foot
Cervical kyphosis

Cardiac anomalies
Cardiac defects are similar to those associated with Marfans syndrome, a disorder of the connective tissue.
Elongation of aorta
Bicuspid aortic valve
Subaortic stenosis
Mitral valve prolapse with mitral regurgitation
Atrial septal defect
Patent ductus arteriosus
Tricuspid valve prolapse
Aortic dissection and aneurysm
Aneurysm of ductus arteriosus

Other reported symptoms
These symptoms were found in rare cases of Larsen syndrome. Cataracts
Cleft palate
Extra bones of wrist
Malocclusion
Microdontia and hypodontia
Complete agenesis of anus
Bifid uterus
Bifid tongue

Causes
Mutations in gene encoding filamin B
Filamins are cytoplasmic proteins that regulate the structure and activity of the cytoskeleton. These proteins serve as scaffolds on which intracellular signaling and protein trafficking are organized. Filamin B has been found to be expressed in human growth plate chondrocytes, which are especially important in vertebrae segmentation and skeleton morphogenesis. Genetic analysis of patients with Larsen syndrome has found the syndrome is caused by missense mutations in the gene that codes for filamin B. These mutations cause an accelerated rate of apoptosis in the epiphyseal growth plates of individuals with the mutation. The defects can cause short stature and other symptoms associated with Larsen syndrome. Localization
Genetic analysis has found that a gene linked to Larsen syndrome, LAR1, is strongly linked to chromosome 3p markers. The locus of this gene is found in a region defined distally by D3S1581 and proximally by D3S1600. This location can be mapped to chromosome region 3p21.1-14.1. Human type VII collagen gene is found within this region in chromosome region 3p21.1. It is reasonable to believe that the joint abnormalities and cardiac anomalies associated with Larsen syndrome are related to the fact that the human type VII collagen gene is found within the same chromosome region as the LAR1 gene.