autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 6

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions 6 is a rare genetic disorder characterized by the accumulation of multiple large deletions of mtDNA in patients' tissues. This condition typically presents with adult-onset weakness of the external eye muscles and exercise intolerance.

The disease is genetically heterogeneous, meaning that it can be caused by mutations in different genes. In some cases, adPEO with mitochondrial DNA deletions 6 has been associated with mutations in the DNA2 gene (601810.0001-601810.0003) [13].

Clinical features of this condition may include:

• Adult-onset weakness of the external eye muscles
• Exercise intolerance
• Muscle weakness
• Signs and symptoms of spinocerebellar ataxia, such as impaired gait and dysarthria

It's worth noting that adPEO with mitochondrial DNA deletions 6 is a rare condition, and more research is needed to fully understand its characteristics and genetic causes.

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a condition characterized by weakness of the eye muscles, which can lead to drooping eyelids (ptosis). The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance. Additional symptoms are variable, but may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.

The first sign of adPEO is typically drooping eyelids (ptosis), which can affect one or both eyelids. As ptosis worsens, affected individuals may experience impaired eye movements, leading to frozen eyes without diplopia. Other manifestations can include fatigue, muscle weakness, and bulbar dysfunction.

It's worth noting that the pattern of inheritance for adPEO is autosomal dominant, meaning that a single copy of the altered gene in each cell is sufficient to cause the disorder. This means that if one parent has the condition, each child has a 50% chance of inheriting it.

References: * [1] The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance. Both autosomal dominant and autosomal recessive inheritance can occur; autosomal recessive inheritance is usually more severe (Filosto et al., 2003; Luoma et al ...). * [7] The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance. * [8] The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance. Both autosomal dominant and autosomal ... * [9] Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. * [4] The first sign of progressive external ophthalmoplegia is typically drooping eyelids (ptosis), which can affect one or both eyelids. As ptosis worsens, affected ...

Based on the search results, here are some diagnostic tests for autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions:

• Genetic testing: Genetic tests can be used to identify mutations in the POLG gene, which is associated with autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions. [1][2]
• Deletion/duplication analysis: This test can be used to detect deletions or duplications of mitochondrial DNA, which are characteristic of this condition. [3][4]
• Multiplex Ligation-dependent Probe Amplification (MLPA): MLPA is a technique that can be used to detect deletions or duplications of specific genes, including those associated with autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions. [5]

It's worth noting that genetic testing and deletion/duplication analysis are typically performed by specialized laboratories, such as Intergen, which offers clinical molecular genetics tests for this condition. [6][7]

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a rare genetic disorder that affects the muscles responsible for eye movements. While there is no specific cure for adPEO, various treatments can help manage its symptoms.

Current Treatment Options:

• Symptomatic treatment: This involves managing the symptoms of adPEO, such as muscle weakness and fatigue, through physical therapy, exercise, and other supportive measures [1].
• Mitochondrial-targeted therapies: These are experimental treatments that aim to improve mitochondrial function in patients with adPEO. However, more research is needed to determine their efficacy and safety [2].
• Antioxidant therapy: Some studies suggest that antioxidant therapy may help reduce oxidative stress and improve symptoms in patients with adPEO [3].

Genetic Testing and Counseling:

• Genetic testing: This can help confirm the diagnosis of adPEO and identify the specific genetic mutation responsible for the condition.
• Counseling: Genetic counseling can provide individuals and families affected by adPEO with information about the condition, its inheritance pattern, and the risks of passing it on to future generations.

Important Considerations:

• No cure available: Currently, there is no cure for adPEO, and treatment focuses on managing symptoms.
• Individualized approach: Treatment plans should be tailored to each patient's specific needs and circumstances.
• Multidisciplinary care: A team of healthcare professionals, including neurologists, geneticists, and physical therapists, may be involved in the management of adPEO.

References:

[1] Suomalainen et al. (1997) - Autosomal dominant progressive external ophthalmoplegia with multiple deletions of mtDNA: clinical, biochemical, and molecular genetic features of the 10q-linked disease [4]. [2] Zeviani et al. (1989) - Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome [5]. [3] Lim et al. (2021) - RRM2B mitochondrial DNA maintenance defects should be suspected in individuals

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions can be challenging to diagnose, and a thorough differential diagnosis is essential. Here are some conditions that may present similarly:

• Mitochondrial myopathies: These are a group of disorders caused by mutations in the mitochondrial DNA, leading to muscle weakness and other symptoms.
• Kearns-Sayre syndrome: This is a rare disorder characterized by progressive external ophthalmoplegia, pigmentary retinopathy, and heart block.
• Chronic progressive external ophthalmoplegia (CPEO): This is a milder form of PEO that typically presents in adulthood.
• Myoclonus epilepsy with ragged-red fibers: This is a rare disorder characterized by myoclonic seizures, muscle weakness, and the presence of ragged-red fibers on muscle biopsy.

These conditions can be distinguished from adPEO with mitochondrial DNA deletions based on their clinical presentation, genetic testing, and other diagnostic features. For example:

• Kearns-Sayre syndrome is typically associated with pigmentary retinopathy and heart block, whereas adPEO is not.
• CPEO tends to present in a milder form than adPEO and may have a later age of onset.
• Myoclonus epilepsy with ragged-red fibers is characterized by myoclonic seizures and the presence of ragged-red fibers on muscle biopsy.

A thorough diagnostic evaluation, including clinical examination, genetic testing, and other investigations, is essential to distinguish adPEO with mitochondrial DNA deletions from these conditions [1][2][3][4].

References:

[1] Suomalainen A. Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions. In: PEOA1 (157640). 1997.

[2] Filosto M. Progressive external ophthalmoplegia (PEO) with multiple mitochondrial DNA (mtDNA) deletions in muscle can be inherited as a dominant or a recessive trait. 2003.

[3] Zeviani M, et al. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med 320: 1293–1299. 1989.

[4] Suomalainen A, Majander A, Haltia M, et al. Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia. J Clin Invest 1992; 90:61–66.