Is Larsen syndrome hereditary?

Larsen syndrome is a genetic condition that is primarily inherited in an autosomal dominant pattern, meaning a single copy of the mutated gene is sufficient to cause the disorder. While it can be passed down from an affected parent, a significant number of cases arise from de novo (spontaneous) mutations that occur for the first time in an individual with no prior family history.

Is Larsen syndrome hereditary?

Yes, Larsen syndrome is a hereditary condition, though the term "hereditary" refers to the passing of a genetic mutation from parents to offspring, while "genetic" refers to the fact that the disease is caused by changes in DNA. In most cases, Larsen syndrome is caused by mutations in the FLNB gene, which provides instructions for making a protein called filamin B. This protein is essential for the development of the skeleton and the formation of joints. Because the condition follows an autosomal dominant inheritance pattern, an affected parent has a 50% chance of passing the causative mutation to each of their children.

How common are de novo mutations in Larsen syndrome?

It is important to note that many individuals diagnosed with Larsen syndrome do not have a family history of the condition. In these instances, the disorder is the result of a de novo mutation. This means the genetic change occurred spontaneously in the egg or sperm cell or during early embryonic development. For families with a child affected by a de novo mutation, the risk of having another child with Larsen syndrome is generally considered low, though germline mosaicism—where a parent carries the mutation in some of their reproductive cells—remains a rare possibility that should be discussed with a genetic counselor.

What genetic testing and counseling are available?

Genetic testing is the gold standard for confirming a diagnosis of Larsen syndrome. Clinical geneticists typically recommend molecular genetic testing, such as targeted gene analysis or multigene panels, to identify pathogenic variants in the FLNB gene. Genetic counseling is highly recommended for all affected families to navigate the complexities of inheritance and reproductive options. Our DiseaseMaps.org community, which includes 58 members living with this condition, often highlights the value of these consultations in understanding long-term care and family planning.

What options exist for family planning and prenatal diagnosis?

For individuals or couples who have been diagnosed with Larsen syndrome and are planning a pregnancy, several options can provide clarity and support:

• Genetic Counseling: A session with a certified genetic counselor can help calculate specific recurrence risks based on family history and test results.


• Prenatal Diagnosis: For known mutations, amniocentesis or chorionic villus sampling (CVS) can be performed during pregnancy to test the fetus for the FLNB mutation.


• Preimplantation Genetic Testing (PGT): If using In Vitro Fertilization (IVF), embryos can be screened for the specific familial mutation before implantation to ensure the child does not inherit Larsen syndrome.


• Carrier Testing: While Larsen syndrome is autosomal dominant, testing family members can help identify those who may have mild or atypical features of the condition.

Next steps

• Consult with a clinical geneticist to confirm a diagnosis via FLNB gene sequencing.


• Connect with the 58 members of the Larsen syndrome community at DiseaseMaps.org to share experiences and coping strategies.


• Schedule a genetic counseling session to discuss reproductive options and recurrence risks.


• Monitor for common skeletal and joint complications under the guidance of an orthopedic specialist.

Medical disclaimer: This content is for educational purposes only and should not replace professional medical advice, diagnosis, or treatment; always seek the guidance of your physician or qualified health provider with any questions regarding a medical condition.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Larsen Syndrome.


• Orphanet: Larsen Syndrome (ORPHA:491).


• OMIM (Online Mendelian Inheritance in Man): Larsen Syndrome; LRSN (Entry #150250).


• PubMed/NCBI: GeneReviews on Filamin B-related disorders.