MYH3 Gene

Freeman-Sheldon syndrome is a condition that primarily affects the face, hands, and feet. People with this disorder have a distinctive facial appearance including a small mouth (microstomia) with pursed lips, giving the appearance of a "whistling face." For this reason, the condition is sometimes called "whistling face syndrome."

People with Freeman-Sheldon syndrome may also have a prominent forehead and brow ridges, a sunken appearance of the middle of the face (midface hypoplasia), a short nose, a long area between the nose and mouth (philtrum), deep folds in the skin between the nose and lips (nasolabial folds), full cheeks, and a chin dimple shaped like an "H" or "V".

Affected individuals may have a number of abnormalities that affect the eyes. These may include widely spaced eyes (hypertelorism), deep-set eyes, outside corners of the eyes that point downward (down-slanting palpebral fissures), a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), and eyes that do not look in the same direction (strabismus).

Other facial features that may occur in Freeman-Sheldon syndrome include an unusually small tongue (microglossia) and jaw (micrognathia) and a high arch in the roof of the mouth (high-arched palate). People with this disorder may have difficulty swallowing (dysphagia), a failure to gain weight and grow at the expected rate (failure to thrive), and respiratory complications that may be life-threatening. Speech problems are also common in this disorder. Some affected individuals have hearing loss.

Freeman-Sheldon syndrome is also characterized by joint deformities (contractures) that restrict movement. People with this disorder typically have multiple contractures in the hands and feet at birth (distal arthrogryposis). These contractures lead to permanently bent fingers and toes (camptodactyly), a hand deformity in which all of the fingers are angled outward toward the fifth finger (ulnar deviation, also called "windmill vane hand"), and inward- and downward-turning feet (clubfoot). Affected individuals may also have a spine that curves to the side (scoliosis).

People with Freeman-Sheldon syndrome also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain. A particular type of muscle relaxant may also trigger the reaction. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless they are treated promptly.

Intelligence is unaffected in most people with Freeman-Sheldon syndrome, but approximately one-third have some degree of intellectual disability.