What is Freeman Sheldon Syndrome?
This is a rare hereditary disorder that is categorized by several contractures – such as restricted movement around two (2) or more areas of the body. It also includes anomalies of the face and head area, defects of the feet and hands and skeletal malformations. This condition or syndrome also may be referred to by several different names such as:
- Craniocarpotarsal dystrophy or dysplasia
- Whistling face syndrome
- Distal Arthrogryposis type 2A
- Whistling face – windmill vane hand syndrome
For the purposes of this article we will use the full name or FSS.
Freeman Sheldon Syndrome Symptoms
Usual symptoms of FSS consist of drooping upper eyelids, low-set ears, strabismus, a long philtrum, scoliosis, gradual hearing loss, and difficulties walking. Gastric reflux has been seen thru infancy but typically recovers with age. A small tongue is present and this limits movements of the soft palate causing nasal speech. Often there is a Y or an H fashioned skin dimpling over the chin.
A more complete list of symptoms and signs referred to in various resources on FSS includes the symptoms below:
- Full forehead
- Small mouth
- Mask-like face
- Broad nasal bridge
- Deep-set eyes
- Epicanthal folds
- Small nose
- Hypoplastic nostrils
- Long philtrum
- H-shaped chin dimple
- High palate
- Ulnar deviation of hands
- Small tongue
- Limited palatal movement with nasal speech
- Cortical thumbs
- Thick skin over flexor surface of proximal phalanges
- Flexion of fingers
- Contracted toes
- Vertical talus
- Contracture of hip
- Contracture of shoulder
- Inguinal hernia
- Contracture of knee
- Incomplete descent of testes
- Postnatal growth deficiency
- Breech birth
- Failure to thrive
- Speech difficulty
- Premature birth
- Whistling appearance of mouth
- Feeding difficulties
- Nasal speech
- Ulnar deviation
- Thickening of skin over proximal phalanges
- Small stature
- Crossed eyes
- Abnormal curvature of the spine
- Round forehead
- Intercostal myopathy
- Flat face
- Full cheeks
- Thickened skin over first finger
- Flared nostrils
- 2nd-5th fingers flexed towards thumb
- Undescended testes
- Contracted thumbs
Freeman Sheldon Syndrome Causes
FSS may be caused by mutations in the MYH3 gene. This gene provides the directions for manufacture of the protein referred to as “embryonic skeletal muscle myosin heavy chain 3”. This is a protein belonging to a protein group called myosin that has involvement in movement of cells and the transference of resources inside and among cells. Myosin as well as an additional protein known as actin are the main mechanisms of fibers of the muscle and are vital for muscle contraction or muscle tensing. “Embryonic skeletal muscle MYH3” forms part of a complex of myosin protein that is working prior to birth and is vital for development normally of the muscles.
This gene mutation that causes FSS most likely interrupts the task of the “embryonic skeletal muscle myosin heavy chair 3” protein, and decreases the capacity of fetal muscle cells to contract. This impairment of muscle contraction can restrict muscle developing in the fetus, causing the contractures and other muscle and skeletal abnormalities linked with FSS. It is unclear exactly how MYH3 gene mutations might cause other features of this disorder.
Some individuals with FSS do not have this mutation in the MYHE gene and in these cases, the cause of FSS is not known.
FSS can have diverse forms of inheritance. In some cases, FSS is congenital in an “autosomal dominant pattern”, meaning that one (1) copy of the changed gene in every cell is enough to create the condition. FSS may also have an autosomal recessive pattern, which indicates that both reproductions of the gene in every cell have mutations. The individual’s parents with an autosomal recessive heritage each carry one copy of the gene that is mutated, but normally they do not show any symptoms or signs of the condition.
But there are some cases where the inheritance pattern is unknown.
Freeman Sheldon Syndrome Diagnosis
A diagnosis of FFS can be made by ultrasonographic assessment in a fetus as small as only 20-week old. This would normally be done in a fetus if there is a positive family history. Then any features that are abnormal can usually be seen. If there is no family history the diagnosis may be made by visible signs after the infant is born.
Freeman Sheldon Syndrome Treatment
Patients must have consultation early with orthopedic and craniofacial surgeons if clubfoot, craniofacial or correction of hand is needed to improve aesthetics or function. Operation measures need to be carefully pursued with avoidance of drastic procedures and consideration carefully of the muscle physiology that is abnormal in FSS.
Many surgical methods have outcomes which are suboptimal, secondary to the myopathy of FSS.
When any surgery measures are going to be done, it needs to be planned as early in life as possible, with the consideration of the tendency of fragile health. Interventions that are early hold the best probability to minimize any delays of development and need to negate the need of having to relearn any basic functions.
Because of abnormal physiology of muscles in FSS, measures that are therapeutic might have unfavorable outcomes. There might be difficulties with endotracheal intubations and access to vein can cause complications.
Patients as well as the parents need to receive psychotherapy that includes marriage counseling. Moderation of lasting psychological problems, such as depression which is caused by chronic illness and PTSD, can be extremely successful if taken care of when there is early intervention. This care can be obtained from the family’s primary care physician or other physician on the patient’s team or referred to other specialist when appropriate. Studies suggest predisposal for psychopathology in pediatric patients with chronic illness. It is advocated that psychiatry preventive support is necessary to enable stability of both negative and positive stressors linked with chronic FSS.
General health maintenance needs to be emphasized in FSS. Emphasis needs to be on preventive or limiting contact to communicable diseases due to the abnormalities to the musculoskeletal system making recovery from even routine infections more problematic in FSS. Bronchitis and pneumonitis often happen after seemingly mild infections of the upper respiratory tract.
Freeman Sheldon Syndrome Prognosis
There is scarce data on prognosis of FSS. There are rare cases of patients dying during infancy from respiratory failure. Otherwise, life expectancy for those with FSS is measured to be normal when general health maintenance is followed.
Freeman Sheldon Syndrome Life Expectancy
Life span and intelligence with FSS are normal. But swallowing difficulties as well as vomiting can lead to failure to thrive during infancy and in some cases retarded growth can occur. Surgical treatment can improve any facial appearances and functioning of feet and hands.
Malignant hyperthermia or MH is a very rare severe problem which is normally activated by contact to certain medications used for general anesthesia; precisely, unstable anesthetic mediators and the neuromuscular obstructive agent, succinylcholine. Those with FSS are considered to be susceptible to this problem as these medications can create an uncontrolled and extreme increase is skeletal muscle oxidative absorption which overpowers the body’s ability to provide oxygen, eliminate carbon dioxide, and to control body temperature which ultimately leads to circulatory failure and death if not quickly treated.