• Disease Overview
  • Synonyms
  • Subdivisions
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
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  • Complete Report

Arthrogryposis Multiplex Congenita


Last updated: 11/16/2023
Years published: 1986, 1988, 1990, 1991, 1997, 1999, 2010, 2013, 2016, 2019, 2023


NORD gratefully acknowledges Judith G. Hall, OC, MD, FCAHS, FRSC, Professor Emerita of Pediatrics and Medical Genetics, University of British Columbia & Children’s and Women’s Health Centre of British Columbia, Department of Pediatrics, BC’s Children’s Hospital, for assistance in the preparation of this report.

Disease Overview

Arthrogryposis is a general or descriptive term for the development of nonprogressive contractures affecting one or more areas of the body prior to birth (congenitally). A contracture is a condition in which a joint becomes permanently fixed in a bent (flexed) or straightened (extended) position, completely or partially restricting the movement of the affected joint. When congenital contractures occur only in one body area, it is not referred to as arthrogryposis but rather an isolated congenital contracture. The most common form of an isolated congenital contracture is clubfoot. When arthrogryposis affects two or more different areas of the body, it may be referred to as arthrogryposis multiplex congenita (AMC). The most common form of AMC is amyoplasia. Arthrogryposis and arthrogryposis multiplex congenita are sometimes used interchangeably.

The symptoms of AMC are present at birth. However, specific symptoms and physical findings can differ greatly in range and severity from one person to another, even within a family. Most affected infants have contractures of various joints. The joints of the legs and arms are usually affected; the legs are affected more often than the arms. The joints of the shoulders, elbows, knees, wrists, ankles, fingers, toes and/or hips are also commonly affected. In addition, the jaws and back may also be affected in individuals with AMC. In most cases, AMC occurs randomly, for no apparent reason (sporadic). More than 400 different conditions can cause isolated or multiple contractures and the causes, genetics, specific symptoms and severity of these disorders vary dramatically. Variants in over 400 genes have been identified as responsible for different types of arthrogryposis. These can be grouped by tissue, affected part of a cell involved and function.

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  • AMC
  • arthrogryposis
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  • amyoplasia
  • distal arthrogryposis
  • ptergium syndrome
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Signs & Symptoms

The most common universal symptom of AMC is limited or absent movement around small and large joints (contractures). The contractures are present at birth (congenital). The muscles of the affected limbs may be underdeveloped (hypoplastic), resulting in a tube-shaped limb with a soft, doughy feeling. Soft tissue webbing may develop over the affected joints.

In addition to joint abnormalities, other findings occur with greater frequency in individuals with AMC. These include abnormally slender and fragile long bones of the arms and legs and cleft palate, a condition in which the roof of the mouth fails to fuse together leaving a groove across the top of the mouth. In males, the testes may fail to descend into the scrotum (cryptorchidism). Intelligence may or may not be affected. Approximately one-third of individuals with AMC may have structural or functional abnormalities of the central nervous system.

Additional symptoms associated with AMC are related to the underlying disorder that causes the condition in each individual. The specific symptoms and their severity can vary dramatically based upon the underlying cause. Two of the most common forms of AMC are amyoplasia and a group of genetic disorders called the distal arthrogryposes.

Amyoplasia is the most common form of AMC. Amyoplasia is a disorder characterized by multiple contractures of the joints. The shoulders may be internally rotated and drawn inward (adducted), the elbows are usually extended, and the wrists are usually flexed. Most affected individuals have fingers that are flexed and stiff. Although in most reports, the distal joints (i.e., those joints farthest away from the center of the body) are usually more severely affected, the shoulders and hips (which are proximal joints) often have significant contractures. Affected individuals usually have severe clubfoot. Some affected individuals may have dislocated hips. In some patients, a birthmark (a splotchy reddish birthmark also called a “stork mark”) may be found at birth on the face. Individuals with amyoplasia usually have normal intelligence, no significant craniofacial abnormalities and no other serious abnormalities of internal organs (visceral abnormalities). However, about 10% of individuals with amyoplasia have abdominal abnormalities such as gastroschisis (a condition in which a hole is present in the wall of the abdomen allowing the intestines to intrude out of the abdominal space) or intestinal atresia (blockage of the intestine). Another 10% have squashed or missing distal fingers or toes. Amyoplasia is common in one of monozygotic twins. Amyoplasia appears to be sporadic and usually does not recur in families. The diagnosis of amyoplasia is clinical currently.

The distal arthrogryposes are a specific subgroup of AMC. This subgroup is characterized by multiple congenital contractures. Common symptoms include contractures of two or more areas of the body, less involvement of the proximal joints (those joints closest to the center of the body) and highly variable expressivity, which means that specific symptoms vary greatly even among individuals with the same disorder and even in the same family. At least 10 different forms of distal arthrogryposis have been identified including Freeman-Sheldon syndrome, Gordon syndrome, trismus-pseudocamptodactyly syndrome, multiple pterygium syndrome and Sheldon-Hall syndrome. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) Most types of distal arthrogryposis have associated known gene mutations.

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The cause of AMC depends on the specific type. For many types, the cause is not fully understood. Arthrogryposis or AMC is not a specific diagnosis, but a physical finding that can be associated with numerous disorders and conditions. AMC is thought to be related to decreased movement in utero, which can have multiple causes. Neurologic and muscle problems may well be the most common causes of decreased fetal movement, but connective tissue disorders, maternal illness and limited space are also common causes. Some cases of AMC occur as part of rare genetic disorders that are inherited. Some cases of AMC are related to multiple factors including genetic and environmental ones (multifactorial inheritance).

AMC may occur as part of certain single-gene disorders that can be inherited in an autosomal recessive, autosomal dominant or X-linked pattern. AMC may also occur as part of chromosomal disorders (e.g., trisomy 18, many microdeletions and microduplications). AMC can also occur as part of certain connective tissue disorders. In addition, some cases of AMC may occur due to abnormalities or disorders associated with improper developmental of the central nervous system or the peripheral nervous system or as part of intrinsic muscle disorders. These disorders may be genetic or may occur due to environmental factors.

The primary underlying mechanism that leads to congenital contractures is believed to be decreased fetal movement during pregnancy. The joints begin to develop in a fetus around five or six weeks into pregnancy. Motion is essential for the proper development of fetal joints. A lack of fetal movement allows for excess connective tissue to form around the joints, which can result in the joint becoming fixed and/or limiting the movement of a joint. In theory, any factor that diminishes or restricts fetal movement can cause congenital contractures. Such factors would include fetal crowding (in which there is not enough room for the fetus to move around) such as when there are multiple births or uterine structural abnormalities. Restricted fetal movement can also occur secondary to maternal disorders including viral infections, drug use, trauma or other maternal illnesses. Low levels of amniotic fluid around the fetus (oligohydramnios) have also been linked to decreased fetal movement.

Amyoplasia, the most common form of AMC, occurs randomly (sporadically). The distal arthrogryposes, another common form of AMC, are usually inherited in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of a mutated gene is necessary to cause the disease. The mutated gene can be inherited from either parent or can be the result of a changed gene in the affected individual. The risk of passing the mutated gene from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.

Central and peripheral nervous system disorders that are associated with AMC include a condition in which the brain and spinal cord do not close before birth (meningomyelocele), the spinal muscular atrophies, and disorders in which there is incomplete development of certain portions of the brain (e.g., anencephaly, hydranencephaly or holoprosencephaly). Most of these disorders develop due to multiple factors including genetic and environmental ones (multifactorial inheritance).

Less often, AMC may be associated with certain muscle disorders including muscular dystrophies, certain mitochondrial disorders and a variety of genetic muscle disorders that are present at birth (congenital myopathies). Such disorders are usually inherited.

Abnormalities affecting the development of connective tissue can cause AMC as well. Connective tissue is the material between the cells of the body that gives tissues form and strength. The abnormal development of connective tissue in the joints can restrict fetal movements, potentially causing multiple contractures. A lack of joint development or the abnormal fusion of bones (synostosis) that are normally separate have also been associated with multiple congenital contractures. Several disorders, which are associated with abnormalities of connective tissue development, have been associated with multiple congenital contractures including diastrophic dysplasia, metatropic dwarfism, popliteal pterygium syndrome and Larsen syndrome.

AMC can also be associated with severe hypotonia (lax muscles with little strength).

In many patients with AMC, the exact underlying cause of the contractures cannot be identified.

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Affected populations

The number of males and females affected by AMC is approximately equal. The condition has been reported in individuals of Asian, African and European descent. Isolated congenital contractures affect approximately 1 in 500 individuals in the general population. AMC affects approximately 1 in 3,000 individuals.

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A diagnosis of AMC is made based upon identification of characteristic symptoms (e.g., multiple congenital contractures), a detailed patient history and a thorough clinical evaluation. Certain tests may be necessary to determine the underlying cause of AMC including nerve conduction, electromyography and muscle biopsy, which can help diagnose neuropathic or myopathic disorders. A nerve conduction study measures how rapidly nerves carry an electrical impulse. Electromyography is a test that records electrical activity in skeletal voluntary muscles at rest and during muscle contraction. A biopsy is a procedure in which a small amount of affected tissue (e.g., muscle) is removed and studied under a microscopic to detect characteristic changes or findings that can aid in obtaining a diagnosis. Imaging studies of the central nervous system (CNS) and genetic tests including comparative genomic hybridization (CGH) array, microarray, and exome studies may also be useful studies in making a diagnosis. Because variants in many genes can lead to arthrogryposis, whole genome sequencing is often required (preferably in both parents for comparison as well) to make a diagnosis.

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Standard Therapies

The treatment of AMC is directed toward the specific findings that are apparent in each individual. A multidisciplinary approach is best. Standard physical therapy, which can improve joint motion and avoid muscle atrophy in the newborn period is beneficial. Gentle joint manipulation and stretching exercises may also be beneficial. Removable splints for the knees and feet that permit regular muscle movement and exercise are also recommended. Serial casting to mobilize stiff joints is helpful.

In some patients, surgery may be necessary to achieve better positioning and increase the range of motion in certain joints, especially the ankles, knees, hips, elbows or wrists. Rarely, tendon transfers have been performed to improve muscle function. Tendons are the tissue by which muscle is attached to bone. A multidisciplinary approach is desirable for best long-term results, including pediatrician, neurologist, orthopedist, rehabilitation physician and therapist and medical geneticist.

Genetic counseling may be recommended for affected individuals and their families. Other treatments are symptomatic and supportive.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

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Hall JG. Arthrogryposes (Multiple Congenital Contractures). In: Emery and Rimoin’s Principle and Practice of Medical Genetics, 6th Ed. Rimoin DL, Connor JM, Pyeritz RE, Korf BR, eds., Churchill Livingstone: New York, 2012.

Hall JG. Arthrogryposis. In: Management of Genetic Syndromes, 3rd Ed. Cassidy SB, Allanson JE eds., John Wiley & Sons: Hoboken, NJ, 2010; 81-96.

Jones KL. Ed. Smith’s Recognizable Patterns of Human Malformation. 6th ed. Elsevier Saunders, Philadelphia, PA; 2006:774-777.

Bamshad M. Arthrogryposis Multiplex Congenita. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:155.

Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:1524-1525.

Staheli L T, Hall JG, Jaffe K M, Paholke DO. Arthrogryposis: a text atlas. Cambridge University Press; Cambridge, UK,1998.

Dahan-Oliel N and Hall J, ed. Special Issue on Interdisciplinary Care for Arthrogryposis. AJMG 2019; 181 (3): i, 269-478.

Erratum in: Am J Med Genet 2015;167A:2866. Ogranovich, Alga [corrected to Ogranovich, Alga]; Pontén, Ava [corrected to Pontén, Eva].

Hall JG, Agranovich O, Pontén E, van Bosse HJ. Summary of the 2nd International Symposium on Arthrogryposis, St. Petersburg, Russia, September 17-19, 2014. Am J Med Genet 2015;167A:1193-1195.

Hall, JG. Oligohydramnios sequence revisited in relationship to arthrogryposis, with distinctive skin changes. Am J Med Genet 2014;164A:2775-2792.

Hall JG, Aldinger KA, Tanaka, KI. Amyoplasia revisited. Am J Med Genet 2014;164:700-730.

Hall JG. Arthrogryposis (Multiple Congenital Contractures): Diagnostic Approach to Etiology, Classification, Genetics, and General Principles. Eur J Med Genet 2014;57:464-472.

Filges I, Hall JG. Failure to identify antenatal multiple congenital contractures and fetal akinesia—proposal of guidelines to improve diagnosis. Prenat Diag 2013;33:61-74.

Hall JG. Uterine structural anomalies and arthrogryposis-death of an urban legend. Am J Med Genet 161A 2012;82-88.

Lowry RB, Sibbald B, Bedard T, Hall JG. Prevalence of multiple congenital contractures including arthrogryposis multiplex congentia in Alberta, Canada and a strategy for classification and coding. Birth Defects Res A Clin Mol Teratol 2010;88:1057-1061.

Dillon ER, Bjornson KF, Jaffe KM, Hall JG, Song K. Ambulatory activity in youth with arthrogryposis: a cohort study. J Pediatr Orthop. 2009;29:214-217.

Hall JG. Pena Shokeir Phenotype (Fetal akinesia deformation sequence) Revisited. Birth Defects Res A, 2009;85:677-694.

Bamshad M, van Heest AE, Pleasure D. Arthrogryposis: a review and update. J Bone Joint Surg Am. 2009;91:40-46.

Fassier A, Wicart P, Dubousset J, Seringe R. Arthrogryposis multiplex congenita. Long-term follow-up from birth until skeletal maturity. J Child Orthop. 2009;3:383-390.

Bevan WP, Hall JG, Bamshad M, et al. Arthrogryposis multiplex congenita (amyoplasia): an orthopaedic perspective. J Pediatr Orthop. 2007;27:594-600.

Bernstein RM. Arthrogryposis and amyoplasia. J Am Acad Orthop Surg. 2002;10:417-424.

Sells JM, Jaffe KM, Hall JG. Amyoplasia, the most common type of arthrogryposis: the potential for good outcome. Pediatrics. 1996;97:225-231.

Lal MK. Arthrogryposis. Medscape. Updated: Aug 30, 2021. Available at: https://emedicine.medscape.com/article/941917-overview Accessed Nov 6, 2023.

Genetic and Rare Disease Information Center (GARD). Arthrogryposis Multiplex Congenita (AMC). Last updated: Last Updated: February 2023. Available at: Arthrogryposis multiplex congenita – About the Disease – Genetic and Rare Diseases Information Center (nih.gov) Accessed Nov 6, 2023.

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