Background
- Arthrogryposis, or arthrogryposis multiplex congenita (AMC), comprises nonprogressive conditions characterized by multiple joint contractures found throughout the body at birth.[1]
- The term is currently used in connection with a very heterogeneous group of disorders that all include the common feature of multiple congenital joint contractures.[2]
Pathophysiology
- The major cause of arthrogryposis is fetal akinesia (ie, decreased fetal movements) due to fetal abnormalities (eg, neurogenic, muscle, or connective tissue abnormalities; mechanical limitations to movement) or maternal disorders (eg, infection, drugs, trauma, other maternal illnesses). Generalized fetal akinesia can also lead to polyhydramnios, pulmonary hypoplasia, micrognathia, ocular hypertelorism, and short umbilical cord.
- During early embryogenesis, joint development is almost always normal. Motion is essential for the normal development of joints and their contiguous structures; lack of fetal movement causes extra connective tissue to develop around the joint. This results in fixation of the joint, limiting movement and further aggravating the joint contracture. Contractures secondary to fetal akinesia are more severe in patients in whom the diagnosis is made early in pregnancy and in those who experience akinesia for longer periods of time during gestation.
Epidemiology
Frequency
United States
- The frequency is about 1 in 3,000 live births.[3, 4]
International
- Arthrogryposis multiplex congenita is more common in isolated populations such as Finland and the Bedouin community in Israel.[5]
Mortality/Morbidity
- The life span of affected individuals depends on the disease severity and associated malformations but is usually normal.
- About 50% of patients with limb involvement and CNS dysfunction die in the first year of life.
- Scoliosis may compromise respiratory function.
Race
- No racial predilection has been described.
Sex
- Males are primarily affected in X-linked recessive disorders; otherwise, males and females are equally affected.
Age
- Arthrogryposis is detectable at birth or in utero using ultrasonography.
Taricco LD, Aoki SS. Rehabilitation of an adult patient with arthrogryposis multiplex congenita treated with an external fixator. Am J Phys Med Rehabil. May 2009;88(5):431-4. [Medline].
Bamshad M, Van Heest AE, Pleasure D. Arthrogryposis: a review and update. J Bone Joint Surg Am. Jul 2009;91 Suppl 4:40-6. [Medline].
Hall JG. Genetic aspects of arthrogryposis. Clin Orthop. 1985;194:44-53. [Medline].
Darin N, Kimber E, Kroksmark AK, Tulinius M. Multiple congenital contractures: birth prevalence, etiology, and outcome. J Pediatr. Jan 2002;140(1):61-7. [Medline].
Laitinen O, Hirvensalo M. Arthrogryposis multiplex congenita. Ann Paediatr Fenn. 1966;12:133-138.
Bevan WP, Hall JG, Bamshad M, Staheli LT, Jaffe KM, Song K. Arthrogryposis multiplex congenita (amyoplasia): an orthopaedic perspective. J Pediatr Orthop. Jul-Aug 2007;27(5):594-600. [Medline].
Alves PV, Zhao L, Patel PK, Bolognese AM. Arthrogryposis: diagnosis and therapeutic planning for patients seeking orthodontic treatment or orthognathic surgery. J Craniofac Surg. Jul 2007;18(4):838-43. [Medline].
Narkis G, Landau D, Manor E, Ofir R, Birk OS. Genetics of Arthrogryposis: Linkage Analysis Approach. Clin Orthop Relat Res. Dec 28 2006;[Medline].
Narkis G, Ofir R, Landau D, Manor E, Volokita M, Hershkowitz R. Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinsitol pathway. Am J Hum Genet. Sep 2007;81(3):530-9. [Medline].
Hall JG. Arthrogryposis multiplex congenita: etiology, genetics, classification, diagnostic approach, and general aspects. J Pediatr Orthop B. Jul 1997;6(3):159-66. [Medline].
Bamshad M, Jorde LB, Carey JC. A revised and extended classification of the distal arthrogryposes. Am J Med Genet. Nov 11 1996;65(4):277-81. [Medline].
Chen H. Multiple Pterygium Syndrome. In: Atlas of Genetic Diagnosis and Counseling. Totowa, New Jersey: Human Press; 2006:702-7.
Chen H, Chang CH, Misra RP. Multiple pterygium syndrome. Am J Med Genet. 1980;7(2):91-102. [Medline].
Escobar V, Bixler D, Gleiser S, Weaver DD, Gibbs T. Multiple pterygium syndrome. Am J Dis Child. Jun 1978;132(6):609-11. [Medline].
Hall JG. The lethal multiple pterygium syndromes. Am J Med Genet. Apr 1984;17(4):803-7. [Medline].
Hall JG, Reed SD, Greene G. The distal arthrogryposes: delineation of new entities--review and nosologic discussion. Am J Med Genet. Feb 1982;11(2):185-239. [Medline].
Entezami M, Runkel S, Kunze J, Weitzel HK, Becker R. Prenatal diagnosis of a lethal multiple pterygium syndrome type II. Case report. Fetal Diagn Ther. Jan-Feb 1998;13(1):35-8. [Medline].
Chen H. Fetal Akinesia Sequence. In: Atlas of Genetic Diagnosis and Counseling. Totowa, New Jersey: Human Press; 2006:398-402.
Chen H, Immken L, Lachman R. Syndrome of multiple pterygia, camptodactyly, facial anomalies, hypoplastic lungs and heart, cystic hygroma, and skeletal anomalies: delineation of a new entity and review of lethal forms of multiple pterygium syndrome. Am J Med Genet. Apr 1984;17(4):809-26. [Medline].
Chen H. Freeman-Sheldon Syndrome. In: Atlas of Genetic Diagnosis and Counseling. Totowa, New Jersey: Human Press; 2006:427-30.
Chen H, Blumberg B, Immken L. The Pena-Shokeir syndrome: report of five cases and further delineation of the syndrome. Am J Med Genet. Oct 1983;16(2):213-24. [Medline].
Chen H, Blackburn WR, Wertelecki W. Fetal akinesia and multiple perinatal fractures. Am J Med Genet. Feb 13 1995;55(4):472-7. [Medline].
Hall JG. Analysis of Pena Shokeir phenotype. Am J Med Genet. Sep 1986;25(1):99-117. [Medline].
Moessinger AC. Fetal akinesia deformation sequence: an animal model. Pediatrics. Dec 1983;72(6):857-63. [Medline].
Staheli LT, Hall JG, Jaffe K, et al. Arthrogryposis: A Text Atlas. New York: Cambridge University Press; 1998.
Navti OB, Kinning E, Vasudevan P, Barrow M, Porter H, Howarth E. Review of perinatal management of arthrogryposis at a large UK teaching hospital serving a multiethnic population. Prenat Diagn. Jan 2010;30(1):49-56. [Medline].
[Guideline] Michaud LJ. Prescribing therapy services for children with motor disabilities. Pediatrics. Jun 2004;113(6):1836-8. [Medline].
Atkins RM, Bell MJ, Sharrard WJ. Pectoralis major transfer for paralysis of elbow flexion in children. J Bone Joint Surg [Br]. Aug 1985;67(4):640-4. [Medline].
Axt MW, Niethard FU, Doderlein L. Principles of treatment of the upper extremity in arthrogryposis multiplex congenita type I. J Pediatr Orthop B. Jul 1997;6(3):179-85. [Medline].
Bamshad M, Bohnsack JF, Jorde LB, Carey JC. Distal arthrogryposis type 1: clinical analysis of a large kindred. Am J Med Genet. Nov 11 1996;65(4):282-5. [Medline].
Banker BQ. Neuropathologic aspects of arthrogryposis multiplex congenita. Clin Orthop. Apr 1985;(194):30-43. [Medline].
Baty BJ, Cubberley D, Morris C, Carey J. Prenatal diagnosis of distal arthrogryposis. Am J Med Genet. Mar 1988;29(3):501-10. [Medline].
Bayne LG. Hand assessment and management of arthrogryposis multiplex congenita. Clin Orthop. Apr 1985;(194):68-73. [Medline].
Beals RK. The distal arthrogryposes: a new classification of peripheral contractures. Clin Orthop Relat Res. Jun 2005;203-10. [Medline].
Bennett JB, Hansen PE, Granberry WM. Surgical management of arthrogryposis in the upper extremity. J Pediatr Orthop. May-Jun 1985;5(3):281-6. [Medline].
Bianchi DW, Van Marter LJ. An approach to ventilator-dependent neonates with arthrogryposis. Pediatrics. 1994;94:682-686. [Medline].
Bui TH, Lindholm H, Demir N, Thomassen P. Prenatal diagnosis of distal arthrogryposis type I by ultrasonography. Prenat Diagn. Dec 1992;12(12):1047-53. [Medline].
Carlson WO, Speck GJ, Vicari V. Arthrogryposis multiplex congenita. A long-term follow-up study. Clin Orthop. Apr 1985;(194):115-23. [Medline].
Chen H. Lethal Multiple Pterygium Syndrome. In: Atlas of Genetic Diagnosis and Counseling. Totowa, New Jersey: Human Press; 2006:604-12.
Chen H. Arthrogryposis Multiplex Congenita. In: Atlas of Genetic Diagnosis and Counseling. Totowa, New Jersey: Humana Press; 2006:74-83.
Chen H, Blackburn WR, Wertelecki W. Fetal akinesia and multiple perinatal fractures. Am J Med Genet. Feb 13 1995;55(4):472-7. [Medline].
Chen H, Blumberg B, Immken L, Lachman R, Rightmire D, Fowler M. The Pena-Shokeir syndrome: report of five cases and further delineation of the syndrome. Am J Med Genet. Oct 1983;16(2):213-24. [Medline].
Dudkiewicz I, Achiron R, Ganel A. Prenatal diagnosis of distalarthrogryposis type 1. Skeletal Radiol. 1999;28:233-235.
Gericke GS, Hall JG, Nelson MM, Beighton PH. Diagnostic considerations in arthrogryposis syndromes in South Africa. Clin Genet. Feb 1984;25(2):155-62. [Medline].
Gordon N. Arthrogryposis multiplex congenita. Brain Dev. Oct 1998;20(7):507-511. [Medline].
Guidera KJ, Drennan JC. Foot and ankle deformities in arthrogryposis multiplex congenita. Clin Orthop. Apr 1985;(194):93-8. [Medline].
Hahn G. Arthrogryposis. Pediatric review and habilitative aspects. Clin Orthop. Apr 1985;(194):104-14. [Medline].
Hall JG. An approach to congenital contractures (arthrogryposis). Pediatr Ann. Jul 1981;DA - 19811025(7):15-26. [Medline].
Hall JG. An approach to research on congenital contractures. Birth Defects Orig Artic Ser. 1984;20(6):8-30. [Medline].
Hall JG. Arthrogryposes (multiple congenital contractures). In: Principles and Practice of Medical Genetics. Vol 2. 1990:989-1035.
Hall JG. Re: distal arthrogryposis in two sisters born to different fathers [Hwu etal. 2004. Am J Med Genet 125A:100-101.]. Am J Med Genet A. Aug 1 2005;136(4):415. [Medline].
Hall JG. The lethal multiple pterygium syndromes. Am J Med Genet. Apr 1984;17(4):803-7. [Medline].
Hall JG, Reed SD, Driscoll EP. Part I. Amyoplasia: a common, sporadic condition with congenital contractures. Am J Med Genet. Aug 1983;15(4):571-90. [Medline].
Hall JG, Reed SD, McGillivray BC. Part II. Amyoplasia: twinning in amyoplasia--a specific type of arthrogryposis with an apparent excess of discordantly affected identical twins. Am J Med Genet. Aug 1983;15(4):591-9. [Medline].
Hall JG, Reed SD, Rosenbaum KN, Gershanik J, Chen H, Wilson KM. Limb pterygium syndromes: a review and report of eleven patients. Am J Med Genet. Aug 1982;12(4):377-409. [Medline].
Hall JG, Reed SD, Scott CI. Three distinct types of X-linked arthrogryposis seen in 6 families. Clin Genet. Feb 1982;21(2):81-97. [Medline].
Huurman WW, Jacobsen ST. The hip in arthrogryposis multiplex congenita. Clin Orthop. Apr 1985;(194):81-6. [Medline].
Hwu WL, Chien YH, Hsu CC. Distal arthrogryposis in two sisters born to different fathers. Am J Med Genet A. Feb 15 2004;125(1):100-1. [Medline].
Jiang M, Bian C, Li X, Man X, Ge W, Han W. Molecular prenatal diagnosis for hereditary distal arthrogryposis type 2B. Prenat Diagn. May 2007;27(5):468-70. [Medline].
Jiang M, Zhao X, Han W, Bian C, Li X, Wang G. A novel deletion in TNNI2 causes distal arthrogryposis in a large Chinese family with marked variability of expression. Hum Genet. Sep 2006;120(2):238-42. [Medline].
Kroksmark AK, Kimber E, Jerre R, Beckung E, Tulinius M. Muscle involvement and motor function in amyoplasia. Am J Med Genet Part A. Aug 15 2006;140(16):1757-67. [Medline].
Letts M, Davidson D. The role of bilateral talectomy in the management of bilateral rigid clubfeet. Am J Orthop. Feb 1999;28(2):106-10. [Medline].
Letts M, Davidson D. The role of bilateral talectomy in the management of bilateral rigid clubfeet. Am J Orthop. Feb 1999;28(2):106-10. [Medline].
McGillivray K, Watson AJ. Congenital arthrogryposis in pregnancy. J Obstet Gynaecol. Mar 2002;22(2):218-9. [Medline].
Mennen U. Arthrogryposis multiplex congenita: functional classification and the AMC disc-o-gram. J Hand Surg [Br]. Aug 2004;29(4):363-7. [Medline].
Mennen U, van Heest A, Ezaki MB. Arthrogryposis multiplex congenita. J Hand Surg [Br]. Oct 2005;30(5):468-74. [Medline].
Mennen U, van Heest A, Ezaki MB, Tonkin M, Gericke G. Arthrogryposis multiplex congenita. J Hand Surg [Br]. Oct 2005;30(5):468-74. [Medline].
Moerman P, Fryns JP. The fetal akinesia deformation sequence. A fetopathological approach. Genet Couns. 1990;1(1):25-33. [Medline].
Murray C, Fixsen JA. Management of knee deformity in classical arthrogryposis multiplex congenita (amyoplasia congenita). J Pediatr Orthop B. Jul 1997;6(3):186-91. [Medline].
Palmer PM, MacEwen GD, Bowen JR, Mathews PA. Passive motion therapy for infants with arthrogryposis. Clin Orthop Relat Res. Apr 1985;(194):54-9. [Medline].
Porter HJ. Lethal arthrogryposis multiplex congenital (fetal akinesia deformation sequence, FADS). Pediatr Pathol Lab Med. Jul-Aug 1995;15(4):617-37. [Medline].
Sells JM, Jaffe KM, Hall JG. Amyoplasia, the most common type of arthrogryposis: the potential for good outcome. Pediatrics. Feb 1996;97(2):225-31. [Medline].
Shrimpton AE, Hoo JJ. A TNNI2 mutation in a family with distal arthrogryposis type 2B. Eur J Med Genet. Mar-Apr 2006;49(2):201-6. [Medline].
Sodergard J, Hakamies-Blomqvist L, Sainio K. Arthrogryposis multiplex congenita: perinatal and electromyographic findings, disability, and psychosocial outcome. J Pediatr Orthop B. Jul 1997;6(3):167-71. [Medline].
St Clair HS, Zimbler S. A plan of management and treatment results in the arthrogrypotic hip. Clin Orthop Relat Res. Apr 1985;(194):74-80. [Medline].
Staheli LT, Chew DE, Elliott JS. Management of hip dislocations in children with arthrogryposis. J Pediatr Orthop. Nov-Dec 1987;7(6):681-5. [Medline].
Sung SS, Brassington AM, Grannatt K, Rutherford A, Whitby FG, Krakowiak PA. Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes. Am J Hum Genet. Mar 2003;72(3):681-90. [Medline].
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. Am J Hum Genet. Jul 2003;73(1):212-4. [Medline].
Thomas B, Schopler S, Wood W, Oppenheim WL. The knee in arthrogryposis. Clin Orthop Relat Res. Apr 1985;(194):87-92. [Medline].
Thompson GH, Bilenker RM. Comprehensive management of arthrogryposis multiplex congenita. Clin Orthop. Apr 1985;(194):6-14. [Medline].
Williams PF. Management of upper limb problems in arthrogryposis. Clin Orthop Relat Res. Apr 1985;(194):60-7. [Medline].

