Larsen Syndrome

Description

Larsen Syndrome is a rare skeletal disorder characterized by abnormalities in the development of joints, particularly in the arms, legs, and spine. This condition can present with a variety of symptoms, ranging from mild to severe, affecting mobility and overall health. This blog delves into the intricacies of Larsen Syndrome, covering its causes, diagnosis, management, and the journey of individuals living with this condition.

Genes Involved

Larsen Syndrome is primarily associated with mutations in three specific genes:

RMRP: This gene encodes a component of the mitochondrial RNA processing endoribonuclease, essential for proper function of mitochondria, the cell‘s energy producers. Mutations in RMRP are linked to a more severe form of Larsen Syndrome.
FLNB: This gene produces a protein called filamin B, crucial for the assembly and organization of the cytoskeleton, the cell‘s structural framework. Mutations in FLNB are connected to a milder form of Larsen Syndrome.
DYNC1H1: This gene provides instructions for creating a protein called dynein heavy chain 1, which is part of the motor proteins involved in cell movement and organelle transport. Mutations in DYNC1H1 are linked to a rare form of Larsen Syndrome, sometimes referred to as "Larsen Syndrome with diaphragmatic hernia."

Recognizing the Signs and Symptoms

Larsen Syndrome manifests with a range of symptoms, often noticeable at birth or shortly after. Key signs include:

Dislocated Joints: The most prominent feature is joint dislocations, particularly in the knees, hips, elbows, and shoulders. These dislocations can be present at birth or develop later in childhood.
Short Limbs: Individuals with Larsen Syndrome may have shorter arms and/or legs compared to others of their age.
Deformed Joints: Joints may appear abnormally shaped or angled, impacting mobility and range of motion.
Spinal Abnormalities: Some individuals experience spinal abnormalities like scoliosis (curvature of the spine).
Facial Features: Certain facial features, such as a flattened nose or a small jaw, might be present.

It‘s important to note that the severity of Larsen Syndrome can vary greatly. Some individuals may have milder symptoms and experience limited functional limitations, while others might face more significant challenges related to mobility and daily activities.

Causes

Larsen Syndrome is a genetic condition caused by mutations in specific genes. These mutations disrupt the normal development of cartilage and bone, leading to the characteristic skeletal abnormalities. It‘s important to understand that the exact cause of these mutations remains largely unknown. However, they are believed to be spontaneous, meaning they occur randomly during the formation of sperm or egg cells. In some cases, a family history of Larsen Syndrome might indicate an increased risk of inheritance.

Inheritance/recurrence risk

Inheritance or Recurrence Risk

Larsen Syndrome can be inherited in an autosomal dominant manner, which means that a single copy of the mutated gene from either parent is sufficient to cause the condition. However, the vast majority of cases arise due to spontaneous mutations, meaning they are not inherited from parents.

The risk of recurrence in families with a history of Larsen Syndrome varies depending on the specific gene involved and the mode of inheritance. It‘s essential to consult with a genetic counselor for personalized guidance.

WES Whole Exome Sequencing