Freeman–Sheldon syndrome

Overview

Freeman–Sheldon Syndrome (FSS), also known as cranio-carpo-tarsal dystrophy or "whistling face syndrome," is a rare congenital disorder characterized by multiple contractures (arthrogryposis), craniofacial abnormalities, and skeletal deformities. It is a type of distal arthrogryposis, meaning it primarily affects the distal joints of the limbs. The condition is present at birth and typically affects facial appearance, hand and foot positioning, and overall mobility. Despite physical limitations, cognitive development is usually normal in most individuals with FSS.

Causes

Freeman–Sheldon Syndrome is primarily caused by mutations in the MYH3 gene, which encodes embryonic myosin heavy chain 3—a protein essential for muscle development. The syndrome is most often inherited in an autosomal dominant pattern, though de novo (new) mutations can occur. Rare autosomal recessive inheritance has also been reported in some families. The genetic mutation leads to improper muscle development, resulting in joint contractures and abnormal facial features.

Symptoms

Freeman–Sheldon Syndrome presents with a distinct set of physical features and musculoskeletal abnormalities. Common symptoms include:

Craniofacial Features

• Small mouth with puckered lips (giving a "whistling" appearance)

• Microstomia (small oral opening)

• Deep-set eyes and a prominent forehead

• Small nose and chin (micrognathia)

• Facial muscle contractures causing limited expression

Musculoskeletal Abnormalities

• Multiple joint contractures, particularly in the hands and feet

• Clubfoot (talipes equinovarus)

• Ulnar deviation and camptodactyly (permanently bent fingers)

• Scoliosis (curved spine)

• Short stature

Other Possible Features

• Difficulty feeding in infancy due to small mouth and jaw

• Speech difficulties

• Respiratory issues in severe cases due to chest wall deformities

Diagnosis

Diagnosis of Freeman–Sheldon Syndrome is typically made based on physical features and clinical examination. Diagnostic steps may include:

• Clinical evaluation: Recognition of characteristic craniofacial and limb deformities at birth.

• Genetic testing: Detection of mutations in the MYH3 gene confirms the diagnosis.

• Imaging studies: X-rays or MRI to assess bone and joint abnormalities.

• Functional assessments: Evaluation by orthopedic, speech, and physical therapists to determine the extent of physical limitations.

Treatment

There is no cure for Freeman–Sheldon Syndrome. Treatment is supportive and focused on improving function and quality of life. A multidisciplinary approach is essential. Treatment options include:

Surgical Interventions

• Corrective surgeries for joint contractures (e.g., tendon releases)

• Maxillofacial surgery for microstomia or jaw anomalies

• Clubfoot correction

Therapeutic Support

• Physical therapy: To improve mobility and prevent joint stiffness

• Occupational therapy: For hand function and daily living skills

• Speech therapy: For articulation issues due to oral muscle stiffness

• Nutritional support: For feeding difficulties in infancy

Medical Management

• Monitoring for respiratory complications

• Pain management for joint or skeletal discomfort

Prognosis

The prognosis for individuals with Freeman–Sheldon Syndrome varies depending on the severity of symptoms and access to medical care. Most individuals have a normal life expectancy and cognitive function. With appropriate surgical and rehabilitative interventions, many can achieve significant functional improvement. However, ongoing therapy and medical monitoring are often required throughout life to manage complications and maintain mobility and independence.