Arthrogryposis: Understanding Congenital Joint Contractures
Arthrogryposis refers to a broad clinical finding rather than a single diagnosis. It is defined by the presence of multiple congenital joint contractures—meaning that two or more joints in different areas of the body are stiff or fixed in position from birth.
This condition affects approximately 1 in every 3,000 live births and is a feature of over 300 different disorders. Importantly, it does not imply a specific cause, and careful diagnosis is essential to determine the underlying condition and guide treatment
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Types of Arthrogryposis
Arthrogryposis can be categorized into two main types:
- Isolated Contractures – Affect only one joint or area, such as congenital clubfoot.
- Multiple Congenital Contractures (Arthrogryposis Multiplex Congenita) – Affect multiple parts of the body.
These multiple contractures can be further divided into:
- Amyoplasia
- Distal Arthrogryposes
- Syndromic Arthrogryposis
Each type is associated with unique causes, symptoms, and treatments.
Amyoplasia
Amyoplasia is the most common and well-studied form of arthrogryposis. The term literally means “lack of muscle development.” It is characterized by:
- Internally rotated shoulders
- Extended elbows
- Flexed and deviated wrists
- Stiff fingers and thumbs in the palm
- Extended knees
- Equinovarus (clubfoot) deformities
About 84% of cases involve both upper and lower limbs. Some children also have facial birthmarks or abdominal issues like gastroschisis
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Treatment for Amyoplasia
Treatment involves a multidisciplinary approach:
- Early physical and occupational therapy to improve mobility.
- Splints and braces to position joints correctly.
- Surgical interventions for severe deformities, commonly involving feet, knees, hips, and sometimes elbows and wrists.
Despite the severity, many children with amyoplasia are capable of walking and performing daily activities independently. Around 85% reach this level of function with consistent therapy
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Distal Arthrogryposes (DAs)
Distal arthrogryposes are a group of genetic disorders that mainly affect the hands and feet. These are inherited in an autosomal dominant pattern and involve at least ten subtypes, including:
- DA1 (Distal Arthrogryposis Type 1) – The prototype, with camptodactyly and clubfoot.
- DA2A (Freeman-Sheldon Syndrome) – Also known as “whistling face syndrome” due to a small mouth and puckered lips.
- DA2B (Sheldon-Hall Syndrome) – Similar to DA1 but with distinct facial features.
- DA5 – Includes eye abnormalities like ptosis and strabismus.
- DA7 (Trismus-Pseudocamptodactyly Syndrome) – Limited mouth opening and finger deformities
Genetic Basis
These conditions are caused by mutations in genes that affect muscle contraction, particularly:
- MYH3, MYH8 – Myosin-related
- TPM2, TNNI2, TNNT3 – Troponin and tropomyosin-related
These gene mutations may cause abnormal contractility of muscles, leading to joint stiffness. Some mutations increase muscle tightness, while others may cause weakness.
Syndromic Arthrogryposis and Neurological Causes
When a child with arthrogryposis shows neurological abnormalities, the cause may lie in the central or peripheral nervous system, or muscles themselves.
Central Nervous System Causes
Brain abnormalities like microcephaly or hydranencephaly, or genetic conditions such as Moebius syndrome or trisomy 18, can reduce fetal movement, leading to joint contractures
Neuromuscular Junction Disorders
Some mothers have autoimmune conditions like myasthenia gravis, where antibodies attack fetal muscle receptors. This can cause temporary arthrogryposis in the baby. Treatments such as maternal thymectomy or IVIG can reduce this risk
Muscular and Genetic Disorders
Several muscle disorders contribute to arthrogryposis:
- Congenital Myopathies – Affect muscle structure or signaling (e.g., MYH3 mutations).
- Muscular Dystrophies – Involve progressive weakening, including LMNA mutations.
- Metabolic Conditions – Such as defects in glycosylation or collagen formation.
Electromyography (EMG), genetic testing, and sometimes muscle biopsy are used to identify these causes
Diagnosis and Research Directions
Diagnosis requires careful:
- Clinical assessment including neurological exams
- Imaging (MRI for brain/spine involvement)
- Genetic analysis (panel testing or whole-exome sequencing)
Over 320 genes have been linked to arthrogryposis. Gene Ontology analyses have grouped them into pathways involving:
- Skeletal muscle development
- Neuron projection and axonogenesis
- Schwann cell differentiation
- Glycoprotein biosynthesis
Future of Treatment
Current treatment remains physical therapy, splinting, and surgery. However, future molecular therapies may target:
- Neuromuscular junctions (e.g., acetylcholine receptor enhancers)
- Fetal movement pathways
- Connective tissue fibrosis
There is growing interest in why fibrosis forms around joints during fetal development. Understanding these processes may lead to preventive or regenerative therapies
Conclusion
Arthrogryposis is a diverse and complex group of disorders marked by congenital joint contractures. While early treatment can improve outcomes significantly, a precise diagnosis is critical for proper management and family planning. Ongoing genetic and developmental research continues to shed light on the biological mechanisms, offering hope for future targeted therapies.
Do you have more questions?
Q. What is arthrogryposis?
A. Arthrogryposis is a condition where a child is born with multiple joint contractures, meaning some joints do not move as much as normal and may be stuck in one position.
Q. What causes arthrogryposis?
A. Arthrogryposis can result from a variety of factors including decreased fetal movement, abnormalities of muscles, connective tissues, nerves, or the central nervous system.
Q. Is arthrogryposis genetic?
A. Arthrogryposis can sometimes be genetic, but most cases are sporadic with no clear inheritance pattern.
Q. How common is arthrogryposis?
A. Arthrogryposis occurs in approximately 1 in 3,000 live births.
Q. What joints are most commonly affected by arthrogryposis?
A. The joints most commonly affected are the shoulders, elbows, wrists, hips, knees, and feet.
Q. Are there different types of arthrogryposis?
A. Yes, there are different types, with amyoplasia being the most common form.
Q. What is amyoplasia?
A. Amyoplasia is the most common type of arthrogryposis characterized by severe joint contractures and muscle weakness.
Q. How is arthrogryposis diagnosed?
A. Arthrogryposis is diagnosed through clinical evaluation and imaging studies such as X-rays, and sometimes genetic testing is performed.
Q. What treatments are available for arthrogryposis?
A. Treatments include physical therapy, occupational therapy, splinting, serial casting, and surgical interventions when necessary.
Q. What are the goals of treating arthrogryposis?
A. The goals are to improve joint mobility and strength, enhance function, and enable the child to perform daily activities independently.
Q. Can surgery help in arthrogryposis?
A. Yes, surgery can help by releasing joint contractures, repositioning bones, and improving overall function.
Q. What types of surgeries might be performed for arthrogryposis?
A. Surgeries may include tendon releases, tendon transfers, joint releases, osteotomies, or other corrective procedures.
Q. Is early treatment important in arthrogryposis?
A. Yes, early treatment is important to maximize joint mobility and function as the child grows.
Q. Can children with arthrogryposis lead independent lives?
A. Many children with arthrogryposis can lead independent lives with appropriate treatment and therapy.
Q. Is physical therapy important for children with arthrogryposis?
A. Physical therapy is critical to improve joint motion, muscle strength, and functional ability.
Q. Can orthotics be used in arthrogryposis treatment?
A. Yes, orthotics such as braces or splints are often used to maintain joint positions and assist in mobility.
Q. Is recurrence of joint contractures possible after treatment?
A. Yes, recurrence of joint contractures is possible, especially during periods of rapid growth.
Dr. Mo Athar
