Freeman-Sheldon syndrome is a rare disease with different types of inheritance, which is characterized by damage to the musculoskeletal system. Pathological changes are caused by a mutation of MYH3 on the short arm of chromosome 17. The disease is manifested by multiple contractures of the joints, deformity of the facial skeleton, ulnar deviation of the hands. Diagnosis includes radiography of the skeleton, neurological examination, genetic testing. Treatment involves surgical operations to eliminate bone and joint defects, rehabilitation with the participation of physiotherapists, physical therapy instructors, speech therapists.
ICD 10
Q87.0 Syndromes of congenital anomalies affecting mainly the appearance of the face
General information
The disease was named after the British orthopedic surgeons E. Freeman, J. Sheldon, who in 1938 first described the pathognomonic signs of the syndrome. In the scientific literature, other names of pathology can be found: craniocarpotarsal dysplasia, distal arthrogryposis type 2A /2B, “the face of a whistling person”. There are no statistical data on the prevalence of the disease. The problem does not lose relevance in modern medicine, since external changes are combined with severe functional disorders of the body.
Causes
Distal arthrogryposis occurs when a gene defect affects the short arm of the 17th chromosome at the 17p13.1 locus. This changes the MYH3 gene, which is necessary for the formation of the correct structure of the myosin protein. Most researchers consider Freeman-Sheldon syndrome to be an autosomal dominant disease, but there are still discussions in medicine about the type of inheritance. Predisposing factors have not been established.
Pathogenesis
The mechanism of development of craniocarpotarsal dysplasia remains unclear. Persistent contractures are usually associated with a myosin defect, intrauterine pathologies of differentiation of bone and muscle tissues. Disorders of articulation and chewing can be caused by hypoplasia of the motor branch of the facial nerve. The formation of ulnar deviation is caused by ulnar nerve damage.
Symptoms
Children are born full-term, have a normal body weight. Immediately after birth, typical facial deformities are noticeable. Freeman-Sheldon syndrome is characterized by a small nose with underdeveloped nostrils, an increased distance from the lower line of the nose to the upper lip, widely spaced eyes with an anti-mongoloid incision. A mandatory symptom is a narrowed oral slit, which is complemented by underdevelopment of the lower jaw, a decrease in the size of the tongue.
Due to deformations of the oral slit, patients experience difficulties when eating, they cannot fully chew it. With age, this problem becomes less noticeable. Microstomy creates inconveniences in oral speech, so children often have cases of lag in speech development. Also, patients face aesthetic problems, since the phenotypic manifestations of the syndrome deform the appearance.
The disease is accompanied by multiple skeletal deformities. Patients have at least 2 articular contractures in the distal extremities, most often the mobility of the fingers of the hand is limited. There are also horse foot, clubfoot. Often there are dislocations of the hip joints, curvature of the spine. Over time, there is a persistent ulnar deviation of the hand, which causes damage to the ulnar nerve.
Complications
Freeman-Sheldon syndrome proceeds without involving internal organs in the process, so the somatic health of patients remains satisfactory. However, 91% of patients gradually develop severe degrees of scoliosis, in 62% of cases there is a lag in growth rates, in 31% of children there is a delay in the development of speech and intellectual functions of mild or moderate severity.
Due to the narrow mouth opening and the inability to fully open the mouth, it is often difficult to perform tracheal intubation as part of an anesthetic manual. This causes serious difficulties during the provision of medical care, since patients with Freeman-Sheldon syndrome need numerous orthopedic and plastic surgeries. Cases of muscle rigidity, malignant hyperthermia as complications of anesthesia are also described.
Diagnostics
When examining a patient with an experienced doctor, a preliminary diagnosis can be made already during an external examination, since the syndrome is accompanied by pathognomonic changes in the phenotype. Physical examination also includes a basic check of the neurological status, assessment of the cardiovascular and respiratory systems. Laboratory and instrumental methods are used to confirm the diagnosis:
- Radiography of the skeleton. Radiological changes are diverse: joint dislocations, scoliosis, distal and proximal contractures. Characteristic signs of the syndrome are the vertical orientation of the talus bone, the displacement of the 2nd metatarsal bone posteriorly.
- Ophthalmological examination. With strabismus, the patient undergoes a full examination with a binocular vision test, an assessment of the convergence ability, and a measurement of the angle of strabismus. According to the indications, visometry and computer refractometry are performed.
- Neurological examination. To exclude other causes of muscle contractures and mobility disorders, electromyography, electroneurography, and evoked potentials are prescribed. If development is delayed, a psychologist or a psychiatrist may need to be consulted.
- Genetic tests. Genome sequencing to detect a defect in the MYH3 gene is the main method of confirming the syndrome. The closest relatives of the proband are also subject to examination to establish the variant of inheritance of the trait.
Treatment
Medical care for distal arthrogryposis is a serious task, which is associated with the inability to completely eliminate musculoskeletal abnormalities, the need for a comprehensive approach to rehabilitation and socialization of patients. There are the following areas of treatment for Freeman-Sheldon syndrome:
- Surgical correction. Surgical interventions are carried out at different age intervals in order to eliminate joint contractures, improve the aesthetics of appearance, create conditions for the proper development of facial expressions, articulation.
- The use of orthoses. To minimize difficulties when walking, a variety of orthopedic devices are used. They are selected individually, taking into account the nature and severity of bone deformities.
- Physical therapy. Massage, physical therapy, kinesiotaping are prescribed to increase joint mobility, improve the coordinated work of all departments of the musculoskeletal system.
- Speech therapy correction. Due to the small size of the mouth and difficulties in opening it, most patients suffer from speech defects. To eliminate them as much as possible, long-term work with a children’s speech therapist is required.
- Dental care. Many patients undergo extraction of a part of their teeth in order to reduce the density of the dentition, improve the bite, and facilitate hygienic care of the oral cavity.
Patients suffering from distal arthrogryposis require regular follow-up by several specialists: orthopedic surgeon, clinical geneticist, otolaryngologist and ophthalmologist. Extended occupational examinations are necessary to monitor the state of health, detect the aggravation of musculoskeletal deformities in time, and correct medical and rehabilitation measures as early as possible.
Prognosis and prevention
Pathology does not affect the life expectancy of patients, so the prognosis is relatively favorable. However, despite the improvement of treatment programs, such patients suffer from cosmetic defects, and the progression of the syndrome often ends in disability. Given the unclear nature of inheritance, preventive measures for Freeman-Sheldon disease have not been developed.