Freeman–Sheldon syndrome explained

Freeman–Sheldon syndrome
Synonyms:Distal arthrogryposis type 2A (DA2A), craniocarpotarsal dysplasia, craniocarpotarsal dystrophy, cranio-carpo-tarsal syndrome, whistling face–windmill vane hand syndrome

Freeman–Sheldon syndrome (FSS) is a very rare form of multiple congenital contracture (MCC) syndromes (arthrogryposes) and is the most severe form of distal arthrogryposis (DA).[1] [2] It was originally described by Ernest Arthur Freeman and Joseph Harold Sheldon in 1938.[3] [4]

As of 2007, only about 100 cases had been reported in medical literature.[5]

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. (1998) mapped the distal arthrogryposis multiplex congenita (DA2B; MIM #601680) gene, a syndrome very similar in phenotypic expression to classic FSS, to 11p15.5-pter.[6] [7] Other mutations have been found as well.[8] [9] In FSS, inheritance may be either autosomal dominant, most often demonstrated.[10] [11] [12] or autosomal recessive (MIM 277720).[13] [14] [15] [16] Alves and Azevedo (1977) note most reported cases of DA2A have been identified as new allelic variation.[17] Toydemir et al. (2006) showed that mutations in embryonic myosin heavy chain 3 (MYH3; MIM *160270), at 17p-13.1-pter, caused classic FSS phenotype, in their screening of 28 (21 sporadic and 7 familial) probands with distal arthrogryposis type 2A.[18] [19] In 20 patients (12 and 8 probands, respectively), missense mutations (R672H; MIM *160270.0001 and R672C; MIM *160270.0002) caused substitution of arg672, an embryonic myosin residue retained post-embryonically.[18] [19] [19] Of the remaining 6 patients in whom they found mutations, 3 had missense private de novo (E498G; MIM *160270.0006 and Y583S) or familial mutations (V825D; MIM *160270.0004); 3 other patients with sporadic expression had de novo mutations (T178I; MIM *160270.0003), which was also found in DA2B; 2 patients had no recognized mutations.[18] [19]

Diagnosis

Freeman–Sheldon syndrome is a type of distal arthrogryposis, related to distal arthrogryposis type 1 (DA1).[20] In 1996, more strict criteria for the diagnosis of Freeman–Sheldon syndrome were drawn up, assigning Freeman–Sheldon syndrome as distal arthrogryposis type 2A (DA2A).[2]

On the whole, DA1 is the least severe; DA2B is more severe with additional features that respond less favourably to therapy. DA2A (Freeman–Sheldon syndrome) is the most severe of the three, with more abnormalities and greater resistance to therapy.[2]

Freeman–Sheldon syndrome has been described as a type of congenital myopathy.[21]

In March 2006, Stevenson et al. published strict diagnostic criteria for distal arthrogryposis type 2A (DA2A) or Freeman–Sheldon syndrome. These included two or more features of distal arthrogryposis: microstomia, whistling-face, nasolabial creases, and 'H-shaped' chin dimple.[1]

Management

Surgical and anesthetic considerations

Patients must have early consultation with craniofacial and orthopaedic surgeons, when craniofacial,[22] [23] [24] clubfoot,[25] or hand correction[26] [27] [28] [29] 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.[30] Difficult endotracheal intubations and vein access complicate operative decisions in many DA2A patients, and malignant hyperthermia (MH) may affect individuals with FSS, as well.[31] [32] [33] [34] Cruickshanks et al. (1999) reports uneventful use of non-MH-triggering agents.[35] Reports have been published about spina bifida occulta in anaesthesia management[36] and cervical kyphoscoliosis in intubations.[37]

Medical emphasis

General health maintenance should be the therapeutic emphasis in Freeman–Sheldon syndrome. The focus is on limiting exposure to infectious diseases because the musculoskeletal abnormalities make recovery from routine infections much more difficult in FSS. Pneumonitis and bronchitis often follow seemingly mild upper respiratory tract infections. Though respiratory challenges and complications faced by a patient with FSS can be numerous, the syndrome's primary involvement is limited to the musculoskeletal systems, and satisfactory quality and length of life can be expected with proper care.

Prognosis

There are little data on prognosis. Rarely, some patients have died in infancy from respiratory failure; otherwise, life expectancy is considered to be normal.

Epidemiology

By 1990, 65 patients had been reported in the literature, with no sex or ethnic preference notable.[38] Some individuals present with minimal malformation; rarely patients have died during infancy as a result of severe central nervous system involvement[39] or respiratory complications.[40] Several syndromes are related to the Freeman–Sheldon syndrome spectrum, but more information is required before undertaking such nosological delineation.[41] [42] [43]

Research directions

One research priority is to determine the role and nature of malignant hyperthermia in FSS. Such knowledge would benefit possible surgical candidates and the anaesthesiology and surgical teams who would care for them. MH may also be triggered by stress in patients with muscular dystrophies.[44] Much more research is warranted to evaluate this apparent relationship of idiopathic hyperpyrexia, MH, and stress. Further research is wanted to determine epidemiology of psychopathology in FSS and refine therapy protocols.

Eponym

It is named for British orthopaedic surgeon Ernest Arthur Freeman (1900–1975) and British physician Joseph Harold Sheldon (1893–1972), who first described it in 1938.

Notable Individuals

Melissa Blake (writer) is a writer and disability advocate with Freeman-Sheldon syndrome.[45]

Notes and References

  1. Stevenson . DA . Carey JC . Palumbos J . Rutherford A . Dolcourt J . Bamshad MJ . Clinical characteristics and natural history of Freeman-Sheldon syndrome . Pediatrics . 117 . 3 . 754–62 . March 2006 . 10.1542/peds.2005-1219. 16510655 . 7952828 .
  2. Bamshad M, Jorde LB, Carey JC . A revised and extended classification of the distal arthrogryposes . Am. J. Med. Genet. . 65 . 4 . 277–81 . November 1996 . 8923935 . 10.1002/(SICI)1096-8628(19961111)65:4<277::AID-AJMG6>3.0.CO;2-M .
  3. Freeman. EA. Sheldon JH. 1938. Cranio-carpo-tarsal dystrophy: undescribed congenital malformation. Arch Dis Child. 13. 75. 277–83. 10.1136/adc.13.75.277. 1975576. 21032118.
  4. James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. .
  5. Web site: Freeman Sheldon Syndrome. NORD (National Organization for Rare Disorders). en-US. 2019-09-12.
  6. Krakowiak PA, O'Quinn JR, Bohnsack JF . A variant of Freeman-Sheldon syndrome maps to 11p15.5-pter . . 60 . 2 . 426–32 . 1997 . 9012416 . 1712403 . etal.
  7. Krakowiak PA, Bohnsack JF, Carey JC, Bamshad M . Clinical analysis of a variant of Freeman-Sheldon syndrome (DA2B) . . 76 . 1 . 93–8 . 1998 . 9508073. 10.1002/(SICI)1096-8628(19980226)76:1<93::AID-AJMG17>3.0.CO;2-K.
  8. Sung SS, Brassington AM, Krakowiak PA, Carey JC, Jorde LB, Bamshad M . Mutations in TNNT3 cause multiple congenital contractures: a second locus for distal arthrogryposis type 2B . . 73 . 1 . 212–4 . 2003 . 12865991 . 1180583 . 10.1086/376418 .
  9. Sung SS, Brassington AM, Grannatt K . Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes . . 72 . 3 . 681–90 . 2003 . 12592607 . 1180243 . 10.1086/368294 . etal.
  10. Aalam M, Kühhirt M . [Windmill vane-like finger deformities] . de . Z Orthop Ihre Grenzgeb . 110 . 3 . 395–8 . 1972 . 4263226 .
  11. Jorgenson RJ . M--craniocarpotarsal dystrophy (whistling face syndrome) in two families . Birth Defects Orig. Artic. Ser. . 10 . 5 . 237–42 . 1974 . 4220006 .
  12. Wettstein A, Buchinger G, Braun A, von Bazan UB . A family with whistling-face-syndrome . Hum. Genet. . 55 . 2 . 177–89 . 1980 . 7450762 . 10.1007/BF00291765. 8059018 .
  13. Kousseff BG, McConnachie P, Hadro TA . Autosomal recessive type of whistling face syndrome in twins . . 69 . 3 . 328–31 . 1982 . 10.1542/peds.69.3.328 . 7199706 . 245095688 .
  14. Kaul KK . Whistling face syndrome (craniocarpotarsal dysplasia) . Indian Pediatr . 18 . 1 . 72–3 . 1981 . 7262998 .
  15. Guzzanti V, Toniolo RM, Lembo A . [The Freeman-Sheldon syndrome] . it . Arch Putti Chir Organi Mov . 38 . 1 . 215–22 . 1990 . 2136374 .
  16. Sánchez JM, Kaminker CP . New evidence for genetic heterogeneity of the Freeman-Sheldon syndrome . . 25 . 3 . 507–11 . 1986 . 3789012 . 10.1002/ajmg.1320250312.
  17. Alves AF, Azevedo ES . Recessive form of Freeman-Sheldon's syndrome or 'whistling face' . J. Med. Genet. . 14 . 2 . 139–41 . 1977 . 856233 . 1013533 . 10.1136/jmg.14.2.139.
  18. Toydemir RM, Rutherford A, Whitby FG, Jorde LB, Carey JC, Bamshad MJ . Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome . . 38 . 5 . 561–5 . 2006 . 16642020 . 10.1038/ng1775. 8226091 .

  19. b .0001 c .0002 d .0004 e .0006, .0003
  20. Hall JG, Reed SD, Greene G . The distal arthrogryposes: delineation of new entities—review and nosologic discussion . Am. J. Med. Genet. . 11 . 2 . 185–239 . February 1982 . 7039311 . 10.1002/ajmg.1320110208 .
  21. Vanĕk J, Janda J, Amblerová V, Losan F . Freeman-Sheldon syndrome: a disorder of congenital myopathic origin? . J. Med. Genet. . 23 . 3 . 231–6 . June 1986 . 3723551 . 1049633 . 10.1136/jmg.23.3.231.
  22. Vaitiekaitis AS, Hornstein L, Neale HW . A new surgical procedure for correction of lip deformity in cranio-carpo-tarsal dysplasia (whistling face syndrome) . J Oral Surg . 37 . 9 . 669–72 . September 1979 . 288890 .
  23. Nara T . Reconstruction of an upper lip and the coloboma in the nasal ala accompanying with Freeman-Sheldon syndrome . Nippon Geka Hokan . 50 . 4 . 626–32 . July 1981 . 7316645 .
  24. Ferreira LM, Minami E, Andrews Jde M . Freeman-Sheldon syndrome: surgical correction of microstomia . Br J Plast Surg . 47 . 3 . 201–2 . April 1994 . 8193861 . 10.1016/0007-1226(94)90056-6.
  25. Malkawi H, Tarawneh M . The whistling face syndrome, or craniocarpotarsal dysplasia. Report of two cases in a father and son and review of the literature . J Pediatr Orthop . 3 . 3 . 364–9 . July 1983 . 6874936 . 10.1097/01241398-198307000-00017. 22025528 .
  26. Call WH, Strickland JW . Functional hand reconstruction in the whistling-face syndrome . J Hand Surg Am . 6 . 2 . 148–51 . March 1981 . 7229290 . 10.1016/s0363-5023(81)80168-2.
  27. Martini AK, Banniza von Bazan U . [Hand deformities in Freeman-Sheldon syndrome and their surgical treatment] . de . Z Orthop Ihre Grenzgeb . 121 . 5 . 623–9 . 1983 . 6649810 . 10.1055/s-2008-1053288.
  28. Martini AK, Banniza von Bazan U . [Surgical treatment of the hand deformity in Freeman-Sheldon syndrome] . de . Handchir Mikrochir Plast Chir . 14 . 4 . 210–2 . December 1982 . 6763591 .
  29. Wenner SM, Shalvoy RM . Two-stage correction of thumb adduction contracture in Freeman-Sheldon syndrome (craniocarpotarsal dysplasia) . J Hand Surg Am . 14 . 6 . 937–40 . November 1989 . 2584652 . 10.1016/S0363-5023(89)80040-1.
  30. Aldinger G, Eulert J . [The Freeman-Sheldon Syndrome] . de . Z Orthop Ihre Grenzgeb . 121 . 5 . 630–3 . 1983 . 6649811 . 10.1055/s-2008-1053289.
  31. Laishley RS, Roy WL . Freeman-Sheldon syndrome: report of three cases and the anaesthetic implications . Can Anaesth Soc J . 33 . 3 Pt 1 . 388–93 . 1986 . 3719442 . 10.1007/BF03010755. free .
  32. Munro HM, Butler PJ, Washington EJ . Freeman-Sheldon (whistling face) syndrome. Anaesthetic and airway management . Paediatr Anaesth . 7 . 4 . 345–8 . 1997 . 9243695 . 10.1046/j.1460-9592.1997.d01-90.x. 40852324 .
  33. Yamamoto S, Osuga T, Okada M . [Anesthetic management of a patient with Freeman-Sheldon syndrome] . ja . Masui . 43 . 11 . 1748–53 . 1994 . 7861610 . etal.
  34. Sobrado CG, Ribera M, Martí M, Erdocia J, Rodríguez R . [Freeman-Sheldon syndrome: generalized muscular rigidity after anesthetic induction] . es. Rev Esp Anestesiol Reanim . 41 . 3 . 182–4 . 1994 . 8059048 .
  35. Cruickshanks GF, Brown S, Chitayat D . Anesthesia for Freeman-Sheldon syndrome using a laryngeal mask airway . Can J Anaesth . 46 . 8 . 783–7 . 1999 . 10451140 . 10.1007/BF03013916. free .
  36. Namiki M, Kawamata T, Yamakage M, Matsuno A, Namiki A . [Anesthetic management of a patient with Freeman-Sheldon syndrome] . ja . Masui . 49 . 8 . 901–2 . 2000 . 10998888 .
  37. Vas L, Naregal P . Anaesthetic management of a patient with Freeman Sheldon syndrome . Paediatr Anaesth . 8 . 2 . 175–7 . 1998 . 9549749 . 10.1046/j.1460-9592.1998.00676.x . 37359095 .
  38. Encyclopedia: Freeman-Sheldon syndrome . Orphanet Encyclopedia . Comier-Daire .
  39. Zampino G, Conti G, Balducci F, Moschini M, Macchiaiolo M, Mastroiacovo P . Severe form of Freeman-Sheldon syndrome associated with brain anomalies and hearing loss . Am. J. Med. Genet. . 62 . 3 . 293–6 . March 1996 . 8882790 . 10.1002/(SICI)1096-8628(19960329)62:3<293::AID-AJMG17>3.0.CO;2-F .
  40. Rao SS, Chary R, Karan S . Freeman Sheldon syndrome in a newborn (whistling face)--a case report . Indian Pediatr . 16 . 3 . 291–2 . March 1979 . 110675 .
  41. Fitzsimmons JS, Zaldua V, Chrispin AR . Genetic heterogeneity in the Freeman-Sheldon syndrome: two adults with probable autosomal recessive inheritance . J. Med. Genet. . 21 . 5 . 364–8 . October 1984 . 6502650 . 1049318 . 10.1136/jmg.21.5.364.
  42. Träger D . [Cranio-carpo-tarsal dysplasia syndrome (Freeman-Sheldon syndrome, whistling face syndrome)] . de . Z Orthop Ihre Grenzgeb . 125 . 1 . 106–7 . 1987 . 3577337 . 10.1055/s-2008-1039687.
  43. Simosa V, Penchaszadeh VB, Bustos T . A new syndrome with distinct facial and auricular malformations and dominant inheritance . Am. J. Med. Genet. . 32 . 2 . 184–6 . February 1989 . 2929657 . 10.1002/ajmg.1320320209 .
  44. Litman RS, Rosenberg H . Malignant hyperthermia: update on susceptibility testing . . 293 . 23 . 2918–24 . 2005 . 15956637 . 10.1001/jama.293.23.2918 .
  45. Book: Blake, Melissa . Beautiful people: my thirteen truths about disability . Hachette Go . 2024 . 978-0-306-83042-6 . New York City . English.

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