SNP Shot: Genomic Insights

Freeman-Sheldon syndrome, also known as Freeman-Burian syndrome, is a condition impacting primarily the muscles of the face and skull (craniofacial muscles). It frequently affects the joints of the hands and feet as well. A key characteristic is the presence of contractures, which are permanent tightenings of muscles, skin, tendons, and surrounding tissues that limit movement. Facial contractures in Freeman-Sheldon syndrome often result in a distinctive "whistling face" appearance, due to a small mouth (microstomia) with pursed lips. This has led to the alternative name "whistling face syndrome." Other common facial features include an "H" or "V"-shaped chin dimple and unusually deep creases between the nose and mouth corners (nasolabial folds).

Individuals with Freeman-Sheldon syndrome can exhibit a variety of other facial characteristics. These may include a prominent forehead and brow ridges, a sunken midface (midface hypoplasia), a short nose, a long philtrum (the area between the nose and mouth), and full cheeks. Eye abnormalities are also common, such as widely spaced eyes (hypertelorism), deep-set eyes, downward-slanting outer corners of the eyes (down-slanting palpebral fissures), a narrowed eye opening (blepharophimosis), droopy eyelids (ptosis), and misaligned eyes (strabismus).

Additional features associated with Freeman-Sheldon syndrome may include an unusually small tongue (microglossia) and jaw (micrognathia), and a high-arched palate. People with this syndrome may experience difficulty swallowing (dysphagia), failure to thrive (inadequate weight gain and growth), and potentially life-threatening breathing difficulties. Speech problems and hearing impairment can also occur.

In the hands and feet, contractures in Freeman-Sheldon syndrome can lead to permanently bent fingers and toes (camptodactyly), a hand deformity where fingers angle outward toward the little finger (ulnar deviation, or "windmill vane hand"), and inward- and downward-turning feet (clubfoot). Less commonly, contractures can affect the hips, knees, shoulders, or elbows.

Individuals with Freeman-Sheldon syndrome may also have skeletal abnormalities involving the spine, ribs, or chest. Spinal curvatures like scoliosis (side-to-side), kyphosis (front-to-back), or lordosis (exaggerated lower back curve) are common. Weakness in the muscles between the ribs can impair breathing and coughing. The ribs or breastbone (sternum) may also be abnormally shaped.

Intelligence is typically normal in individuals with Freeman-Sheldon syndrome, although physical abnormalities may cause delays in achieving developmental milestones.

Inheritance:

Freeman-Sheldon syndrome is inherited in an autosomal dominant manner. This means that having only one copy of the altered gene in each cell is enough to cause the condition. Most cases arise from new, spontaneous changes in the gene and occur in families with no prior history of the disorder. Some individuals inherit the altered gene from a parent who is also affected. In rare instances, a parent may carry the gene variant only in some or all of their sperm or egg cells (germline mosaicism), and therefore shows no signs or symptoms of the condition.