Lethal arthrogryposis with anterior horn cell disease

A rare genetic disorder characterized by joint contractures and motor neuron disease

Lethal arthrogryposis with anterior horn cell disease is a rare genetic disorder that is characterized by severe joint contractures and degeneration of the anterior horn cells in the spinal cord. This condition is typically fatal in the neonatal period or shortly after birth.

Pathophysiology

Lethal arthrogryposis with anterior horn cell disease is primarily caused by genetic mutations that affect the development and function of motor neurons. The anterior horn cells, located in the spinal cord, are responsible for transmitting signals from the brain to the muscles, enabling movement. In this disorder, these cells degenerate, leading to muscle weakness and atrophy.

The joint contractures, or arthrogryposis, occur due to the lack of fetal movement in utero, which is a result of the impaired motor neuron function. Without normal movement, the joints become fixed in a bent or extended position.

Genetics

Autosomal recessive inheritance pattern

Lethal arthrogryposis with anterior horn cell disease is inherited in an autosomal recessive pattern. This means that an affected individual must inherit two copies of the mutated gene, one from each parent. Parents of an affected child are typically carriers, meaning they each carry one copy of the mutated gene but do not show symptoms of the disorder.

Clinical Presentation

Infants with this condition are often born with multiple joint contractures, which can affect the limbs, spine, and other parts of the body. The severity of the contractures can vary, but they are usually severe enough to significantly limit movement.

In addition to joint contractures, affected infants may exhibit signs of muscle weakness and atrophy due to the degeneration of anterior horn cells. Respiratory difficulties are common, as the muscles required for breathing may be affected, often leading to early death.

Diagnosis

Diagnosis of lethal arthrogryposis with anterior horn cell disease is based on clinical examination, family history, and genetic testing. Prenatal ultrasound may reveal decreased fetal movement and joint contractures, prompting further investigation.

Genetic testing can confirm the diagnosis by identifying mutations in the genes associated with the disorder. This is important for genetic counseling and family planning.

Management

There is currently no cure for lethal arthrogryposis with anterior horn cell disease. Management focuses on supportive care to improve quality of life and address symptoms. This may include physical therapy to maintain joint mobility and respiratory support to assist with breathing.

Prognosis

The prognosis for individuals with lethal arthrogryposis with anterior horn cell disease is poor. Most affected infants do not survive beyond the neonatal period due to respiratory failure and other complications.

Related pages

• Arthrogryposis
• Spinal muscular atrophy
• Motor neuron disease