SNP Shot: Genomic Insights

Larsen syndrome is a genetic condition that disrupts normal bone development throughout the body. The symptoms of this syndrome vary considerably, even among members of the same family. Individuals with Larsen syndrome are often born with dislocated hips, knees, or elbows. Deformities of the feet, particularly clubfeet, are also frequently observed. X-rays often reveal the presence of small, extra bones in the wrists and ankles of those affected. A characteristic feature is blunt, square-shaped fingertips, especially the thumbs (spatulate thumbs).

Facial characteristics common in individuals with Larsen syndrome include a prominent forehead (frontal bossing), a flattened nasal bridge and midface (midface hypoplasia), and widely spaced eyes (ocular hypertelorism). A cleft palate is present in many individuals with this syndrome. Hearing loss may also occur due to malformations of the small bones in the ears (ossicles).

Short stature is a typical feature of Larsen syndrome. Affected individuals may also exhibit an unusually wide range of joint movement (hypermobility) or restricted movement due to joint deformities (contractures). Curvature of the spine (kyphosis or scoliosis) can also occur, potentially leading to breathing difficulties or compression of the spinal cord, which can cause limb weakness. Some individuals with Larsen syndrome experience respiratory issues such as airway narrowing, brief pauses in breathing (apnea), and frequent respiratory infections. Heart and kidney problems can also occur. Individuals with Larsen syndrome can live into adulthood, and their cognitive abilities are typically unaffected.

Inheritance:

Larsen syndrome is typically inherited in an autosomal dominant manner. This means that only one copy of the mutated gene in each cell is enough to cause the disorder. In some instances, an affected individual inherits the mutation from a parent who also has the condition. However, in other cases, the syndrome arises from a new genetic mutation and occurs in individuals with no family history of the disorder. Autosomal recessive inheritance of Larsen syndrome has been reported, albeit rarely. Autosomal recessive inheritance requires that both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive form of Larsen syndrome each carry one copy of the mutated gene but usually do not display signs or symptoms of the condition. In some of these cases of apparent autosomal recessive inheritance, multiple siblings may each inherit a single altered gene from an unaffected parent who carries an FLNB mutation only in their sperm or egg cells. This phenomenon, where a mutation is present only in reproductive cells, is known as germline mosaicism. Some rarer conditions with similar symptoms that follow an autosomal recessive inheritance pattern were once classified as Larsen syndrome but are now recognized as distinct disorders. These conditions tend to be more severe and are not caused by mutations in the FLNB gene.