autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 3

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions 3 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.

Clinical Features:

• Adult onset of weakness of the external eye muscles
• Exercise intolerance
• Other symptoms may include muscle weakness, fatigue, and shortness of breath

Genetic Heterogeneity: The disease is genetically heterogeneous, meaning that it can be caused by mutations in different genes. According to Hirano and DiMauro (2001), mutations in the ANT1 and C10ORF2 gene account for approximately 4% and 35% of familial adPEO cases, respectively.

DNA Deletions: The condition is characterized by multiple large deletions of mtDNA, which can vary in size and location. These deletions can affect different tissues and organs, leading to a range of symptoms and complications.

Inheritance Pattern: Autosomal dominant inheritance means that a single copy of the mutated gene is sufficient to cause the disease. This means that if one parent has the condition, each child has a 50% chance of inheriting it.

References:

• Hirano and DiMauro (2001) reviewed the molecular genetics of progressive external ophthalmoplegia and classified the specific disease type according to mutation in the autosomal ANT1, C10ORF2, and POLG genes as well as in multiple mitochondrial genes. [3]
• Lamantea et al. (2002) stated that mutations in the ANT1 and C10ORF2 gene account for approximately 4% and 35% of familial adPEO cases. [3]

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions 3, also known as PEOA3, is a rare genetic disorder characterized by weakness of the external eye muscles and exercise intolerance. The most common clinical features include:

• Adult onset of weakness of the external eye muscles: This is typically the first sign of adPEO, which can affect one or both eyelids [4].
• Exercise intolerance: Affected individuals may experience fatigue and muscle weakness during physical activity [7][8].
• Ptosis: Drooping eyelids can occur in some cases, affecting one or both eyelids [9].
• Paralysis of the muscles that control eye movement: This can lead to impaired eye movements and frozen eyes without diplopia [13].
• Impaired swallowing: In some cases, adPEO may also affect the muscles involved in swallowing, leading to difficulties with eating and drinking.
• Weakness of the limbs: Additional symptoms can include muscle weakness in the arms and legs.

It's worth noting that the severity and progression of adPEO can vary widely among affected individuals. Some people may experience mild symptoms, while others may have more severe manifestations [14].

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a rare genetic disorder that affects the muscles responsible for eye movement. Diagnostic tests are essential to confirm the presence of this condition.

Diagnostic Tests:

• Clinical Molecular Genetics test: This test is specifically designed to diagnose adPEO with mitochondrial DNA deletions, autosomal dominant 3. The test uses deletion/duplication analysis and Multiplex Ligation-dependent Probe Amplification (MLPA) offered by Intergen.
• mtDNA next-generation sequencing in blood: This diagnostic test can help identify mutations in the mitochondrial DNA that may be associated with adPEO.

Other Relevant Information:

• The clinical features of adPEO include progressive external ophthalmoplegia, ptosis, and impaired eye movements [8].
• Mutations in numerous nuclear-encoded genes cause autosomal dominant progressive external ophthalmoplegia, including POLG1 [12].

References:

• Intergen's Clinical Molecular Genetics test for Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 [10]
• Zeviani M et al. (1989). Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med 320: 1293–1299. [11]

Understanding Progressive External Ophthalmoplegia (PEO)

Progressive external ophthalmoplegia (PEO) is a rare genetic disorder characterized by muscle weakness, mainly affecting the lower limbs and external eye muscles. The condition can have different inheritance patterns depending on the gene involved.

Causes of PEO

PEO is caused by mutations in mitochondrial DNA, which affects the functioning of mitochondria, the energy-producing structures within cells. The most common clinical features include:

• Muscle weakness, particularly affecting the lower limbs and external eye muscles
• Difficulty swallowing (dysphagia)
• Weakness or paralysis of the face and neck muscles
• Vision problems, including double vision (diplopia)

Types of PEO

There are several types of PEO, including:

• Autosomal dominant progressive external ophthalmoplegia (adPEO): This is the most common type, characterized by muscle weakness and external eye muscle weakness.
• Mitochondrial DNA deletion syndromes: These are caused by deletions in mitochondrial DNA and can lead to a range of symptoms, including muscle weakness, vision problems, and hearing loss.

Genetic Testing

Genetic testing can help diagnose PEO and identify the underlying cause. The most common genetic tests include:

• POLG gene testing
• TWNK gene testing
• RRM2B gene testing

Treatment Options

There is no cure for PEO, but treatment options are available to manage symptoms and improve quality of life. These may include:

• Physical therapy to maintain muscle strength and mobility
• Speech therapy to address swallowing difficulties
• Eye care to manage vision problems
• Medications to alleviate symptoms such as pain and fatigue

References

1. 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.
2. Autosomal dominant progressive external ophthalmoplegia-6 (PEOA6) is characterized by muscle weakness, mainly affecting the lower limbs, external eye muscles, and difficulty swallowing. [3]
3. Progressive external ophthalmoplegia can have different inheritance patterns depending on the gene involved. When the nuclear genes POLG, TWNK, RRM2B, or SLC25A4 are involved, progressive external ophthalmoplegia is usually inherited in an autosomal dominant pattern. [1]
4. Mitochondrial DNA deletion syndromes are caused by deletions in mitochondrial DNA and can lead to a range of symptoms, including muscle weakness, vision problems, and hearing loss. [2]

Note: The references provided are based on the information given in the prompt and may not be an exhaustive list of all relevant studies or sources.

Autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA deletions is a clinical syndrome characterized by ptosis, impaired eye movements, and other systemic features. The differential diagnosis for adPEO involves considering various conditions that may present with similar symptoms.

Key considerations:

• Mitochondrial myopathies: Other mitochondrial diseases, such as Kearns-Sayre syndrome or chronic progressive external ophthalmoplegia (CPEO), can cause similar clinical features.
• Muscular dystrophies: Certain types of muscular dystrophy, like myotonic dystrophy or facioscapulohumeral muscular dystrophy, may present with ptosis and impaired eye movements.
• Neurological disorders: Conditions such as multiple system atrophy, Parkinson's disease, or amyotrophic lateral sclerosis (ALS) can also cause similar symptoms.

Genetic testing:

• TWNK gene mutations: Autosomal dominant