Freeman-Sheldon syndrome
Freeman-Sheldon syndrome is a rare genetic condition primarily affecting the muscles of the face and skull, often resulting in characteristic facial features and joint contractures.
Overview
Freeman-Sheldon syndrome, also known as Freeman-Burian syndrome, is a condition that primarily affects muscles in the face and skull (craniofacial muscles) and can often affect joints in the hands and feet. The condition is characterized by contractures, which are permanent tightenings of muscles, skin, tendons, and surrounding tissues that restrict movement.
Symptoms
Contractures in the face lead to a distinctive appearance, including a small mouth with pursed lips, which gives the appearance of whistling. For this reason, it is sometimes called "whistling face syndrome." Other common features include:
- A chin dimple shaped like an "H" or "V."
- Unusually deep folds in the skin between the nose and the corners of the mouth (nasolabial folds).
- Sunken appearance of the middle of the face.
- Abnormalities of the eyes, such as widely spaced eyes, droopy eyelids (ptosis), and eyes that do not look in the same direction (strabismus).
- An unusually small tongue and jaw, and a high arch in the roof of the mouth.
- Difficulty swallowing (dysphagia), breathing complications, and speech or hearing impairment.
- Hand and foot deformities, such as permanently bent fingers and toes, and "windmill vane hand" (fingers angled toward the fifth finger).
- Abnormal curvature of the spine (scoliosis or kyphosis) or lower back (lordosis).
Intelligence is typically unaffected, though developmental milestones may be delayed due to physical limitations.
Causes & Risk Factors
Freeman-Sheldon syndrome is caused by variants (mutations) in the MYH3 gene. This gene provides instructions for making the myosin-3 protein, which is essential for muscle contraction and normal development of fetal muscle fibers. Genetic changes are thought to disrupt this protein, leading to prolonged muscle contraction and impaired relaxation, which causes the characteristic stiffening of muscles and tissues.
Inheritance
This condition follows an autosomal dominant pattern of inheritance, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases occur as new (de novo) mutations with no family history, though some are inherited from an affected parent.