Freeman–Sheldon syndrome
Freeman–Sheldon syndrome is a very rare form of multiple congenital contracture syndromes and is the most severe form of distal arthrogryposis. It was originally described by Ernest Arthur Freeman and Joseph Harold Sheldon in 1938.
As of 2007, only about 100 cases had been reported in medical literature.
Signs and symptoms
The symptoms of Freeman–Sheldon syndrome include drooping of the upper eyelids, strabismus, low-set ears, a long philtrum, gradual hearing loss, scoliosis and walking difficulties. Gastroesophageal reflux has been noted during infancy, but usually improves with age. The tongue may be small, and the limited movement of the soft palate may cause nasal speech. Often there is an H- or Y-shaped dimpling of the skin over the chin.Cause
FSS is caused by genetic changes. Krakowiak et al. mapped the distal arthrogryposis multiplex congenita gene, a syndrome very similar in phenotypic expression to classic FSS, to 11p15.5-pter. Other mutations have been found as well. In FSS, inheritance may be either autosomal dominant, most often demonstrated. or autosomal recessive. Alves and Azevedo note most reported cases of DA2A have been identified as new allelic variation. Toydemir et al. showed that mutations in embryonic myosin heavy chain 3, at 17p-13.1-pter, caused classic FSS phenotype, in their screening of 28 probands with distal arthrogryposis type 2A. In 20 patients, missense mutations caused substitution of arg672, an embryonic myosin residue retained post-embryonically. Of the remaining 6 patients in whom they found mutations, 3 had missense private de novo or familial mutations ; 3 other patients with sporadic expression had de novo mutations, which was also found in DA2B; 2 patients had no recognized mutations.Diagnosis
Freeman–Sheldon syndrome is a type of distal arthrogryposis, related to distal arthrogryposis type 1. In 1996, more strict criteria for the diagnosis of Freeman–Sheldon syndrome were drawn up, assigning Freeman–Sheldon syndrome as distal arthrogryposis type 2A.On the whole, DA1 is the least severe; DA2B is more severe with additional features that respond less favourably to therapy. DA2A is the most severe of the three, with more abnormalities and greater resistance to therapy.
Freeman–Sheldon syndrome has been described as a type of congenital myopathy.
In March 2006, Stevenson et al. published strict diagnostic criteria for distal arthrogryposis type 2A or Freeman–Sheldon syndrome. These included two or more features of distal arthrogryposis: microstomia, whistling-face, nasolabial creases, and 'H-shaped' chin dimple.
Management
Surgical and anesthetic considerations
Patients must have early consultation with craniofacial and orthopaedic surgeons, when craniofacial, clubfoot, or hand correction is indicated to improve function or aesthetics. Operative measures should be pursued cautiously, with avoidance of radical measures and careful consideration of the abnormal muscle physiology in Freeman–Sheldon syndrome. Unfortunately, many surgical procedures have suboptimal outcomes, secondary to the myopathy of the syndrome.When operative measures are to be undertaken, they should be planned for as early in life as is feasible, in consideration of the tendency for fragile health. Early interventions hold the possibility to minimise developmental delays and negate the necessity of relearning basic functions.
Due to the abnormal muscle physiology in Freeman–Sheldon syndrome, therapeutic measures may have unfavourable outcomes. Difficult endotracheal intubations and vein access complicate operative decisions in many DA2A patients, and malignant hyperthermia may affect individuals with FSS, as well. Cruickshanks et al. reports uneventful use of non-MH-triggering agents. Reports have been published about spina bifida occulta in anaesthesia management and cervical kyphoscoliosis in intubations.