Larsen syndrome

Overview

Larsen syndrome is a rare congenital disorder that primarily affects the development of bones and joints. It is characterized by multiple joint dislocations at birth, distinctive facial features, and skeletal abnormalities. The severity of the condition can vary widely, ranging from mild joint instability to life-threatening complications involving the spine or airways. Larsen syndrome can be inherited in either an autosomal dominant or autosomal recessive pattern, depending on the genetic mutation involved. Early diagnosis and orthopedic management are essential to improve mobility and quality of life.

Causes

Larsen syndrome is most commonly caused by mutations in the FLNB gene, which encodes filamin B, a protein that plays a critical role in organizing the structure of the cell’s cytoskeleton and in skeletal development. The condition can follow different inheritance patterns:

• Autosomal dominant form – caused by mutations in FLNB and generally presents with a wide spectrum of skeletal and joint anomalies.

• Autosomal recessive form – less common, more severe, and may involve other genes yet to be fully identified.

Some cases occur sporadically without a family history, due to new (de novo) mutations.

Symptoms

Clinical features of Larsen syndrome can vary, but common signs and symptoms include:

• Multiple joint dislocations – especially in the hips, knees, and elbows, often noted at birth

• Characteristic facial appearance – flat midface, prominent forehead, depressed nasal bridge, and wide-spaced eyes (hypertelorism)

• Short stature

• Clubfoot (talipes equinovarus)

• Scoliosis or kyphosis – abnormal spinal curvature, which may worsen with age

• Hypermobile joints – leading to instability and early degenerative joint disease

• Hearing loss – in some cases

• Respiratory complications – due to abnormal chest wall development or cervical spine instability

Diagnosis

Diagnosis of Larsen syndrome is based on clinical findings, imaging studies, and genetic testing. Diagnostic procedures may include:

• Physical examination – to assess joint dislocations, facial features, and musculoskeletal abnormalities

• Radiographic imaging – including X-rays and MRI to detect dislocations, spinal abnormalities, and other skeletal defects

• Genetic testing – to identify mutations in the FLNB gene and confirm the diagnosis

• Family history evaluation – to determine inheritance patterns

Treatment

Management of Larsen syndrome requires a multidisciplinary approach and is tailored to the individual’s specific symptoms. Treatment options may include:

• Orthopedic surgery – to correct joint dislocations and stabilize the spine, especially the cervical spine

• Physical and occupational therapy – to improve mobility, strengthen muscles, and enhance joint function

• Bracing and assistive devices – for joint support and mobility assistance

• Monitoring and treatment of spinal issues – including surgical intervention if spinal cord compression is present

• Hearing aids – for individuals with hearing loss

• Airway management – in severe cases with respiratory difficulties

Prognosis

The prognosis for individuals with Larsen syndrome depends on the severity of skeletal and systemic involvement. Many affected individuals lead active lives with appropriate medical care, physical therapy, and surgical interventions. However, complications such as spinal cord compression, respiratory issues, or progressive joint damage can affect quality of life and require long-term monitoring. Early diagnosis and a proactive treatment plan significantly improve functional outcomes and overall prognosis.