Arthrogryposis: Symptoms, Types, Causes and Treatment

Arthrogryposis, most commonly referred to as arthrogryposis multiplex congenita (AMC), is a rare yet complex group of conditions marked by multiple joint contractures present at birth. While its manifestations and severity vary widely, understanding its symptoms, types, causes, and treatment options is crucial for affected individuals, families, and healthcare professionals. This article offers a comprehensive, evidence-based overview of arthrogryposis, synthesizing the latest research and clinical insights.

Symptoms of Arthrogryposis

When a baby is born with arthrogryposis, it can be immediately apparent due to joint stiffness and unusual limb positions. But the symptoms extend far beyond what meets the eye. Knowing the range of symptoms is essential, as they can affect day-to-day function and quality of life. This section explores both the visible and less obvious symptoms experienced by individuals with arthrogryposis.

Symptom	Description	Frequency/Severity	Source(s)
Joint Contractures	Stiffness or limited movement in two or more joints	Hallmark, always present	1 3 6 13 14
Muscle Weakness	Reduced muscle mass, often with atrophy	Common, varies	3 4 13
Deformities	Abnormal limb positions or shapes	Frequent	3 4 13 15
Associated Features	E.g. facial anomalies, short neck, ptosis	Variable, type-dependent	2 3 5
Pain	Chronic or episodic, not always visible	Sometimes severe	3
Psychological Effects	Anxiety, fatigue, altered self-esteem	Often overlooked	3
Respiratory Issues	Restrictive lung disease, especially in DA5	Rare, subtype-specific	3 5

Table 1: Key Symptoms

Joint Contractures: The Defining Symptom

• Joint contractures—reduced range of motion in two or more joints—are the signature feature of arthrogryposis. These contractures usually affect both arms and legs but may involve only the upper or lower limbs in some cases 1 6 13 14.
• The pattern and severity can vary, with some children having mild limitations while others experience significant restrictions affecting daily activities 13 15.

Muscle Weakness and Deformities

• Muscle weakness and atrophy often accompany joint contractures. In amyoplasia (the most common form), muscles may be underdeveloped or replaced with fibrous tissue 3 4 13.
• Limb deformities are common, resulting from imbalanced muscle forces and fixed joints. These may manifest as clubfoot, internally rotated shoulders, or extended elbows 13 15.

Associated Features and Invisible Symptoms

• Some forms present with facial anomalies (e.g., micrognathia, ptosis, short neck), or other congenital changes like cryptorchidism or heart defects 2 3 5.
• Pain and psychological effects (anxiety, fatigue, altered self-esteem, social isolation) are increasingly recognized but are often less visible and under-addressed 3.
• Rarely, respiratory issues may occur, especially in those with certain genetic subtypes (e.g., DA5 with PIEZO2 mutations) 3 5.

Types of Arthrogryposis

Arthrogryposis is not a single disease but a descriptive term that encompasses a spectrum of conditions. Understanding its classification helps guide diagnosis and management, as different types have distinct features and prognoses.

Type	Defining Feature	Prevalence/Notes	Source(s)
Amyoplasia	Severe muscle underdevelopment	Most common (40%+)	1 4 6 11
Distal Arthrogryposis	Predominantly hands/feet affected	Multiple subtypes (DA1-10)	5 6
Syndromic	Part of a larger syndrome, often with CNS involvement	Heterogeneous	6 7 8 9 10
Neurogenic	Caused by nerve or spinal cord issues	Variable, non-progressive	2 4 6
Myopathic	Primary muscle disease	Less common	2 6

Table 2: Major Types of Arthrogryposis

Amyoplasia

• Amyoplasia is the most frequent type, accounting for at least 40% of cases. It features severe muscle underdevelopment, often with fatty or fibrous tissue replacing muscle 1 4 6.
• Typically involves all four limbs, with shoulders internally rotated, elbows extended, and wrists flexed. Clubfoot is common 1 4.

Distal Arthrogryposis

• Distal arthrogryposis (DA) primarily affects the hands and feet. Over ten subtypes exist (DA1-DA10), each with specific clinical and genetic features 5 6.
• DA5 is notable for additional features like ptosis, ophthalmoplegia, and occasional restrictive lung disease, often linked to PIEZO2 mutations 5.

Syndromic Arthrogryposis

• Syndromic cases are part of broader syndromes, often involving other organs or the central nervous system. Over 400 distinct disorders can include arthrogryposis as a feature 6 7 8 9 10.
• Examples include conditions with heart defects, facial anomalies, or neurodevelopmental delays 2 5 9 10.

Neurogenic and Myopathic Types

• Neurogenic arthrogryposis arises from abnormalities in nerves or the spinal cord, leading to muscle weakness and contractures 2 4.
• Myopathic forms are due to primary muscle disease; these are less common and often diagnosed via muscle biopsy 2 6.

Causes of Arthrogryposis

Understanding what leads to arthrogryposis is challenging due to its heterogeneity. However, a unifying factor is reduced fetal movement, or fetal akinesia, which disrupts normal joint and muscle development.

Cause	Mechanism/Description	Commonality	Source(s)
Fetal Akinesia	Reduced/absent fetal movement	Universal factor	6 13 14
Genetic Mutations	Mutations in >220 genes, including PIEZO2, CHRNG, ECEL1	Many cases	5 7 8 9 10
Neuropathic	Spinal cord or nerve abnormalities	Frequent	1 2 4 9 10
Myopathic	Abnormal muscle development/function	Less common	2 6
Mechanical	Limited fetal space (e.g., uterine constraint)	Occasional	1 6
Metabolic/Other	Metabolic/end-plate/vascular disruptions	Rare	1 6

Table 3: Main Causes of Arthrogryposis

Fetal Akinesia: The Common Denominator

• All cases of arthrogryposis share a common pathway: decreased fetal movement. Movement is essential for normal joint and muscle development; when it's absent, contractures form 6 13 14.

Genetic Causes

• Over 220 genes are associated with arthrogryposis, reflecting its genetic complexity 7 8.
• Notable genes include PIEZO2 (implicated in DA5), CHRNG, ECEL1, CNTNAP1, and GPR126. Mutations can affect muscle, nerve, or connective tissue development 5 7 9 10.
• Some cases show oligogenic inheritance, where more than one gene contributes to the phenotype 8.

Neuropathic and Myopathic Mechanisms

• Neuropathic forms result from abnormalities in the spinal cord or peripheral nerves, leading to muscle weakness and joint contractures 1 2 4 9 10.
• Myopathic forms arise from muscle diseases, either due to genetic defects or other disruptions in muscle development 2 6.

Other Contributing Factors

• Mechanical factors, such as limited uterine space (e.g., multiple pregnancies, uterine anomalies), can restrict movement and contribute to contractures 1 6.
• Metabolic, end-plate, and vascular disorders are rare causes but underscore the diversity of potential underlying mechanisms 1 6.

Treatment of Arthrogryposis

Managing arthrogryposis aims to maximize function, independence, and quality of life. Given its complexity, treatment is tailored to the individual and typically requires a multidisciplinary approach.

Approach	Purpose/Intervention	Notes/Outcomes	Source(s)
Early Intervention	Initiate therapy ASAP to improve outcomes	Critical for best results	12 13 14
Physical Therapy	Improve mobility, prevent contractures	Mainstay, lifelong	4 12 13 15
Orthoses/Splints	Support/joint positioning	Often used with therapy	4 12 13
Surgery	Release contractures, correct deformities	Frequently needed	13 14 15
Multidisciplinary Care	Coordinated by team of specialists	Essential for all aspects	11 12 14
Psychological Support	Address mental health & social needs	Increasingly recognized	3 12

Table 4: Summary of Treatment Approaches

Early and Ongoing Intervention

• Early treatment, starting soon after birth, is vital to improve range of motion and prevent secondary complications 12 13 14.
• Physical and occupational therapy are the cornerstones, focusing on stretching, strengthening, and maintaining joint mobility 4 12 13 15.

Orthoses, Splinting, and Assistive Devices

• Splints and orthoses help maintain joint position and function, especially during periods of growth 4 12 13.
• Adaptive devices support independence in daily activities.

Surgical Management

• Surgery is often required to release joint contractures, correct deformities, and restore function—especially in the upper extremities and feet 13 14 15.
• The timing and type of surgery depend on the individual's needs, with the goal of improving function rather than achieving "normal" anatomy 15.

Multidisciplinary and Individualized Care

• Optimal care involves a team: orthopedic surgeons, neurologists, physiatrists, therapists, nurses, and social workers 11 12 14.
• Plans are individualized and adapted over time as the child grows and their needs change 12.

Addressing Invisible and Long-term Needs

• Psychological support is crucial, as issues like chronic pain, fatigue, anxiety, and social isolation can significantly impact quality of life 3 12.
• Long-term follow-up is important, as recurrences of contractures and new challenges can arise 13.

Conclusion

Arthrogryposis is a diverse and complex group of conditions requiring an individualized, human-centered approach. Key insights from current research include:

• Symptoms are dominated by joint contractures and muscle weakness, but invisible symptoms like pain and psychological effects are also significant 1 3 13.
• Types include amyoplasia, distal, syndromic, neurogenic, and myopathic forms, each with distinctive features and implications for care 1 4 5 6.
• Causes are heterogeneous, with decreased fetal movement as a shared pathway, underpinned by a wide range of genetic and environmental factors 5 6 7 8.
• Treatment is multidisciplinary and should start early, combining therapy, orthoses, surgery, and psychological support to maximize independence and quality of life 12 13 14 15.

In summary:

• Arthrogryposis is not a single disease but a descriptive term for multiple congenital contractures
• Early, individualized, and multidisciplinary care improves outcomes
• Both visible and invisible symptoms must be recognized and addressed
• Advances in genetics continue to improve diagnosis, classification, and management strategies

With ongoing research and coordinated care, individuals with arthrogryposis can achieve improved mobility, independence, and quality of life.