Arthrogryposis: Background, Pathophysiology, Epidemiology

Sections

Sections Arthrogryposis
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Follow-up
Media Gallery
References

Overview

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.

Frequency

United States

The frequency is about 1 in 3000 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 central nervous system (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.

Clinical Presentation

Taricco LD, Aoki SS. Rehabilitation of an adult patient with arthrogryposis multiplex congenita treated with an external fixator. Am J Phys Med Rehabil. 2009 May. 88(5):431-4. [Medline].
Bamshad M, Van Heest AE, Pleasure D. Arthrogryposis: a review and update. J Bone Joint Surg Am. 2009 Jul. 91 Suppl 4:40-6. [Medline]. [Full Text].
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. 2002 Jan. 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. 2007 Jul-Aug. 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. 2007 Jul. 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. 2006 Dec 28. [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. 2007 Sep. 81(3):530-9. [Medline].
Hall JG. Arthrogryposis multiplex congenita: etiology, genetics, classification, diagnostic approach, and general aspects. J Pediatr Orthop B. 1997 Jul. 6(3):159-66. [Medline].
Bamshad M, Jorde LB, Carey JC. A revised and extended classification of the distal arthrogryposes. Am J Med Genet. 1996 Nov 11. 65(4):277-81. [Medline].
Chen H. Multiple Pterygium Syndrome. Atlas of Genetic Diagnosis and Counseling. 2nd. New York Dordrecht Heidelberg London: Springer; 2012. 2: 1479-1485.
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. 1978 Jun. 132(6):609-11. [Medline].
Hall JG. The lethal multiple pterygium syndromes. Am J Med Genet. 1984 Apr. 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. 1982 Feb. 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. 1998 Jan-Feb. 13(1):35-8. [Medline].
Chen H. Fetal Akinesia Sequence. Atlas of Genetic Diagnosis and Counseling. 2nd. New York Dordrecht Heidelberg London: Springer; 2012. 2: 809-821.
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. 1984 Apr. 17(4):809-26. [Medline].
Chen H. Freeman-Sheldon Syndrome. Atlas of Genetic Diagnosis and Counseling. 2nd. New York Dordrecht Heidelberg London: Springer; 2012. 2: 883-889.
Chen H, Blumberg B, Immken L. The Pena-Shokeir syndrome: report of five cases and further delineation of the syndrome. Am J Med Genet. 1983 Oct. 16(2):213-24. [Medline].
Chen H, Blackburn WR, Wertelecki W. Fetal akinesia and multiple perinatal fractures. Am J Med Genet. 1995 Feb 13. 55(4):472-7. [Medline].
Hall JG. Analysis of Pena Shokeir phenotype. Am J Med Genet. 1986 Sep. 25(1):99-117. [Medline].
Dicke JM, Piper SL, Goldfarb CA. The utility of ultrasound for the detection of fetal limb abnormalities - a 20-year single-center experience. Prenat Diagn. 2014 Dec 4. [Medline].
Rink BD. Arthrogryposis: a review and approach to prenatal diagnosis. Obstet Gynecol Surv. 2011 Jun. 66(6):369-77. [Medline].
Dimitraki M, Tsikouras P, Bouchlariotou S, Dafopoulos A, Konstantou E, Liberis V. Prenatal assessment of arthrogryposis. A review of the literature. J Matern Fetal Neonatal Med. 2011 Jan. 24(1):32-6. [Medline].
Pakkasjärvi N, Ritvanen A, Herva R, Peltonen L, Kestilä M, Ignatius J. Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland--an epidemiological study. Am J Med Genet A. 2006 Sep 1. 140A(17):1834-9. [Medline].
Lin IW, Chueh HY, Chang SD, Cheng PJ. The application of three-dimensional ultrasonography in the prenatal diagnosis of arthrogryposis. Taiwan J Obstet Gynecol. 2008 Mar. 47(1):75-8. [Medline].
Ajayi RA, Keen CE, Knott PD. Ultrasound diagnosis of the Pena Shokeir phenotype at 14 weeks of pregnancy. Prenat Diagn. 1995 Aug. 15(8):762-4. [Medline].
Scott H, Hunter A, Bédard B. Non-lethal arthrogryposis multiplex congenita presenting with cystic hygroma at 13 weeks gestational age. Prenat Diagn. 1999 Oct. 19(10):966-71. [Medline].
Murphy JC, Neale D, Bromley B, Benacerraf BR, Copel JA. Hypoechogenicity of fetal long bones: a new ultrasound marker for arthrogryposis. Prenat Diagn. 2002 Dec. 22(13):1219-22. [Medline].
Moessinger AC. Fetal akinesia deformation sequence: an animal model. Pediatrics. 1983 Dec. 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. 2010 Jan. 30(1):49-56. [Medline].
Chen H. Arthrogryposis Multiplex Congenita. Atlas of Genetic Diagnosis and Counseling. 2nd. New York Dordrecht Heidelberg London: Springer; 2012. 1: 141-156.
[Guideline] Michaud LJ. Prescribing therapy services for children with motor disabilities. Pediatrics. 2004 Jun. 113(6):1836-8. [Medline].
Nouraei H, Sawatzky B, MacGillivray M, Hall J. Long-term functional and mobility outcomes for individuals with arthrogryposis multiplex congenita. Am J Med Genet A. 2017 May. 173 (5):1270-8. [Medline].
Atkins RM, Bell MJ, Sharrard WJ. Pectoralis major transfer for paralysis of elbow flexion in children. J Bone Joint Surg [Br]. 1985 Aug. 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. 1997 Jul. 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. 1996 Nov 11. 65(4):282-5. [Medline].
Banker BQ. Neuropathologic aspects of arthrogryposis multiplex congenita. Clin Orthop. 1985 Apr. (194):30-43. [Medline].
Baty BJ, Cubberley D, Morris C, Carey J. Prenatal diagnosis of distal arthrogryposis. Am J Med Genet. 1988 Mar. 29(3):501-10. [Medline].
Bayne LG. Hand assessment and management of arthrogryposis multiplex congenita. Clin Orthop. 1985 Apr. (194):68-73. [Medline].
Beals RK. The distal arthrogryposes: a new classification of peripheral contractures. Clin Orthop Relat Res. 2005 Jun. 203-10. [Medline].
Bennett JB, Hansen PE, Granberry WM. Surgical management of arthrogryposis in the upper extremity. J Pediatr Orthop. 1985 May-Jun. 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. 1992 Dec. 12(12):1047-53. [Medline].
Carlson WO, Speck GJ, Vicari V. Arthrogryposis multiplex congenita. A long-term follow-up study. Clin Orthop. 1985 Apr. (194):115-23. [Medline].
Chen H. Lethal Multiple Pterygium Syndrome. Atlas of Genetic Diagnosis and Counseling. 2nd. New York Dordrecht Heidelberg London: Springer; 2006. 2: 1287-1294.
Chen H, Blackburn WR, Wertelecki W. Fetal akinesia and multiple perinatal fractures. Am J Med Genet. 1995 Feb 13. 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. 1983 Oct. 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. 1984 Feb. 25(2):155-62. [Medline].
Gordon N. Arthrogryposis multiplex congenita. Brain Dev. 1998 Oct. 20(7):507-511. [Medline].
Guidera KJ, Drennan JC. Foot and ankle deformities in arthrogryposis multiplex congenita. Clin Orthop. 1985 Apr. (194):93-8. [Medline].
Hahn G. Arthrogryposis. Pediatric review and habilitative aspects. Clin Orthop. 1985 Apr. (194):104-14. [Medline].
Hall JG. An approach to congenital contractures (arthrogryposis). Pediatr Ann. 1981 Jul. 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). Principles and Practice of Medical Genetics. 1990. Vol 2: 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. 2005 Aug 1. 136(4):415. [Medline].
Hall JG. The lethal multiple pterygium syndromes. Am J Med Genet. 1984 Apr. 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. 1983 Aug. 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. 1983 Aug. 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. 1982 Aug. 12(4):377-409. [Medline].
Hall JG, Reed SD, Scott CI. Three distinct types of X-linked arthrogryposis seen in 6 families. Clin Genet. 1982 Feb. 21(2):81-97. [Medline].
Huurman WW, Jacobsen ST. The hip in arthrogryposis multiplex congenita. Clin Orthop. 1985 Apr. (194):81-6. [Medline].
Hwu WL, Chien YH, Hsu CC. Distal arthrogryposis in two sisters born to different fathers. Am J Med Genet A. 2004 Feb 15. 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. 2007 May. 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. 2006 Sep. 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. 2006 Aug 15. 140(16):1757-67. [Medline].
Letts M, Davidson D. The role of bilateral talectomy in the management of bilateral rigid clubfeet. Am J Orthop. 1999 Feb. 28(2):106-10. [Medline].
Letts M, Davidson D. The role of bilateral talectomy in the management of bilateral rigid clubfeet. Am J Orthop. 1999 Feb. 28(2):106-10. [Medline].
McGillivray K, Watson AJ. Congenital arthrogryposis in pregnancy. J Obstet Gynaecol. 2002 Mar. 22(2):218-9. [Medline].
Mennen U. Arthrogryposis multiplex congenita: functional classification and the AMC disc-o-gram. J Hand Surg [Br]. 2004 Aug. 29(4):363-7. [Medline].
Mennen U, van Heest A, Ezaki MB. Arthrogryposis multiplex congenita. J Hand Surg [Br]. 2005 Oct. 30(5):468-74. [Medline].
Mennen U, van Heest A, Ezaki MB, Tonkin M, Gericke G. Arthrogryposis multiplex congenita. J Hand Surg [Br]. 2005 Oct. 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. 1997 Jul. 6(3):186-91. [Medline].
Palmer PM, MacEwen GD, Bowen JR, Mathews PA. Passive motion therapy for infants with arthrogryposis. Clin Orthop Relat Res. 1985 Apr. (194):54-9. [Medline].
Porter HJ. Lethal arthrogryposis multiplex congenital (fetal akinesia deformation sequence, FADS). Pediatr Pathol Lab Med. 1995 Jul-Aug. 15(4):617-37. [Medline].
Sells JM, Jaffe KM, Hall JG. Amyoplasia, the most common type of arthrogryposis: the potential for good outcome. Pediatrics. 1996 Feb. 97(2):225-31. [Medline].
Shrimpton AE, Hoo JJ. A TNNI2 mutation in a family with distal arthrogryposis type 2B. Eur J Med Genet. 2006 Mar-Apr. 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. 1997 Jul. 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. 1985 Apr. (194):74-80. [Medline].
Staheli LT, Chew DE, Elliott JS. Management of hip dislocations in children with arthrogryposis. J Pediatr Orthop. 1987 Nov-Dec. 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. 2003 Mar. 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. 2003 Jul. 73(1):212-4. [Medline].
Thomas B, Schopler S, Wood W, Oppenheim WL. The knee in arthrogryposis. Clin Orthop Relat Res. 1985 Apr. (194):87-92. [Medline].
Thompson GH, Bilenker RM. Comprehensive management of arthrogryposis multiplex congenita. Clin Orthop. 1985 Apr. (194):6-14. [Medline].
Williams PF. Management of upper limb problems in arthrogryposis. Clin Orthop Relat Res. 1985 Apr. (194):60-7. [Medline].

Media Gallery

An infant with amyoplasia. Note internally rotated and adducted shoulders, fixed extended elbows, pronated forearms, flexed wrists and fingers, and severe talipes deformity.
An infant with distal arthrogryposis type I. Note medially overlapping fingers, tightly clenched fists, and positional foot contractures.
The hands of a patient with contractural arachnodactyly (Beals syndrome). Note the long, thin fingers with interphalangeal joint contractures.
A girl with an autosomal recessive type of multiple pterygium syndrome. Note the multiple joint contractures at the knees with marked pterygia, including intercrural webbing, affecting her stance and ambulation.
A mother and child both affected with trismus pseudocamptodactyly. Note the small mouth (with limited ability to open) and flexion contractures of fingers on dorsiflexion.
Twins with a lethal type of autosomal recessive multiple pterygium syndrome. Note the multiple joint contractures with marked pterygia, cardiac and lung hypoplasia, and characteristic facies.
An infant with a lethal type of multiple pterygium syndrome. Note multiple joint contractures with marked pterygia and a cystic hygroma on the posterior aspect of the head and the neck.
The photograph on the left shows an infant with fetal akinesia. Note depressed nasal bridge, micrognathia, flexion contractures of elbows, bilateral clubhands, and arthrogryposis of fingers. The radiograph on the right shows an infant with fetal akinesia. Note gracile ribs; thin, long bones with multiple fractures at mid diaphyses of the humeri, distal diaphyses of the femora, and proximal diaphyses of both tibiae and left fibula; and clubhands.
An infant with Pena-Shokeir syndrome. Note characteristic facies (ocular hypertelorism; short nose with depressed bridge; small and markedly recessed jaw; low-set, malformed ears), short neck, mild contracture at the hip, moderate contractures at elbows and knees, severe ankle contractures, and camptodactyly with ulnar deviation of the hands.

of 9

Sections Arthrogryposis
Overview
Presentation
- History
- Physical
- Causes
- Show All
DDx
Workup
Treatment
Medication
Follow-up
Media Gallery
References

Arthrogryposis

Background

Pathophysiology

Epidemiology

Frequency

Mortality/Morbidity

Race

Sex

Age

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Arthrogryposis

Background

Pathophysiology

Epidemiology

Frequency

Mortality/Morbidity

Race

Sex

Age

References

Tables

Contributor Information and Disclosures

What would you like to print?

Find Us On

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Related Conditions and Diseases

Medscape Consult

News & Perspective

Tools

Most Popular Articles

Recommended