Arthrogryposis, also known as arthrogryposis multiplex congenita (AMC), is a group of conditions present at birth characterized by multiple joint contractures. These contractures limit joint range of motion, causing stiffness or fixation. Severity varies, affecting joint movement throughout the body.
How Arthrogryposis Can Be Genetic
Arthrogryposis often has a genetic basis, with over 400 genes implicated across more than 300 different conditions. Genetic causes are identified in approximately 30% of cases.
Genetic inheritance patterns include autosomal dominant, autosomal recessive, and X-linked recessive forms. For instance, distal arthrogryposis type I is inherited in an autosomal dominant pattern, where one altered gene copy is sufficient. In contrast, conditions like multiple pterygium syndrome (Escobar syndrome) are autosomal recessive, requiring two mutated gene copies.
X-linked recessive inheritance is also observed, where males are more commonly affected, and female carriers may pass the gene to their sons. Mutations in genes like TPM2 and MYBPC1 (active in muscle cells) are linked to distal arthrogryposis type 1. Other genes, like FLNB (involved in the cytoskeleton), are linked to syndromes such as Larsen syndrome.
Factors Beyond Genetics
While genetics account for a portion of arthrogryposis cases, other factors can also contribute. Non-genetic influences primarily involve restricted fetal movement during development. Reduced fetal movement (fetal akinesia) is a common mechanism, leading to extra connective tissue around joints and stiffness.
Maternal illnesses during pregnancy, such as myasthenia gravis, diabetes, or multiple sclerosis, can contribute. In myasthenia gravis, maternal antibodies can cross the placenta, affecting fetal muscle function. Exposure to certain medications or substances, including alcohol and specific drugs, can also contribute.
Environmental factors within the womb, such as limited space, can also cause joint contractures. This can occur due to uterine abnormalities, multiple pregnancies, or oligohydramnios (low amniotic fluid), all restricting fetal movement. These extrinsic factors can cause similar joint contractures even without a genetic component.
Identifying the Cause Through Diagnosis
Determining the underlying cause of arthrogryposis involves a comprehensive diagnostic process. Initial assessment includes a clinical examination to evaluate joint involvement and muscle weakness. Imaging techniques are then employed to further assess the condition.
Prenatal ultrasound can detect reduced fetal movement or joint contractures, usually during the second trimester. Postnatal imaging (X-rays or MRI) visualizes joints, assesses muscle mass, and rules out other conditions.
Genetic testing identifies specific genetic mutations. This involves gene panels (testing for mutations in specific genes associated with arthrogryposis) or whole exome sequencing (WES). WES analyzes a larger portion of the genome to identify unknown genetic causes, which helps understand prognosis and assess recurrence risk.
What a Genetic Diagnosis Means for Families
A genetic diagnosis for arthrogryposis provides families with important information. Genetic counseling is a beneficial step for affected families, offering a deeper understanding of test results. Genetic counselors can explain the specific inheritance pattern of the identified mutation, such as autosomal dominant, autosomal recessive, or X-linked.
Counseling also assesses recurrence risk in future pregnancies, which varies by genetic disorder type. If a specific genetic mutation is identified, prenatal diagnosis options for subsequent pregnancies, including chorionic villus sampling or amniocentesis, may be discussed. These options allow for early detection in future pregnancies.
Beyond medical aspects, a genetic diagnosis offers emotional and practical support. It provides clarity about the condition, connects families with support networks, and guides long-term management and surveillance. While a genetic diagnosis offers valuable insights, arthrogryposis management often involves a multidisciplinary approach focused on improving joint function and quality of life.