autosomal dominant progressive external ophthalmoplegia 1

Autosomal dominant progressive external ophthalmoplegia (adPEO) is a rare genetic disorder characterized by weakness of the external eye muscles, resulting in bilateral ptosis and diffuse symmetric ophthalmoparesis. This condition typically appears in adults between ages 18 and 40 and slowly worsens over time.

The symptoms of adPEO may also include skeletal muscle weakness, cataracts, hearing loss, sensory axonal neuropathy, ataxia, parkinsonism, cardiomyopathy, hypogonadism, and other systemic features. In some cases, the condition can be associated with multiple large deletions of mitochondrial DNA (mtDNA).

AdPEO is caused by heterozygous mutations in the nuclear-encoded DNA polymerase-gamma gene (POLG) on chromosome 15q25. This genetic mutation affects the function of mitochondria, leading to progressive muscle weakness and other systemic symptoms.

It's worth noting that adPEO can be inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the condition. The condition typically affects both males and females equally.

References:

• [1] A rare genetic, neuro-ophthalmological disease characterized by progressive weakness of the external eye muscles, resulting in bilateral ptosis and diffuse symmetric ophthalmoparesis.
• [4] autosomal dominant progressive external ophthalmoplegia (adPEO) with mitochondrial DNA (mtDNA) deletions-1 (PEOA1) is caused by heterozygous mutation in the nuclear-encoded DNA polymerase-gamma gene (POLG; 174763) on chromosome 15q25.
• [13] Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, Parkinsonism, hypogonadism, and cataracts in what has been called “chronic progressive external ophthalmoplegia plus

Autosomal dominant progressive external ophthalmoplegia (adPEO) is a rare genetic disorder that affects the muscles controlling eye movement, leading to a range of signs and symptoms.

Primary Signs:

• Drooping eyelids (ptosis): The first sign of adPEO is typically drooping eyelids, which can affect one or both eyelids [4][5].
• Progressive weakness of external eye muscles: As the condition progresses, affected individuals may experience progressive weakness of the external eye muscles, leading to impaired mobility of the eyes [11][15].

Additional Signs and Symptoms:

• Skeletal muscle weakness: Affected individuals may also experience skeletal muscle weakness, which can affect various parts of the body [7].
• Cataracts: Cataracts are a common feature in adPEO, affecting the lens of the eye [14].
• Hearing loss: Sensorineural hearing loss is another symptom associated with adPEO, caused by nerve damage in the inner ear [12][13].
• Sensory axonal neuropathy: Affected individuals may experience weakness and loss of sensation in the limbs due to nerve damage (neuropathy) [7][13].
• Ataxia: Impaired muscle coordination (ataxia) is another symptom associated with adPEO, affecting balance and movement [7][12].
• Depression: Depression is a common feature in adPEO, often occurring alongside other symptoms [14].
• Parkinsonism: Some individuals may experience parkinsonism, characterized by tremors, stiffness, and slowed movements [12][14].
• Hypogonadism: Affected individuals may also experience hormonal dysfunction (hypogonadism), affecting reproductive health [7][14].

It's essential to note that not all individuals with adPEO will exhibit all of these symptoms. The severity and progression of the condition can vary significantly from person to person.

References: [4] - Context 4 [5] - Context 5 [7] - Context 7 [11] - Context 11 [12] - Context 12 [13] - Context 13 [14] - Context 14 [15] - Context 15

Autosomal dominant progressive external ophthalmoplegia (adPEO) is a mitochondrial disease characterized by accumulation of multiple large deletions of mtDNA [9]. Diagnostic tests for adPEO typically involve genetic testing to identify the underlying cause of the condition.

• Exome Sequencing with CNV Detection: This test method, approved in New York State, can be used to diagnose adPEO by identifying pathogenic variants in the POLG gene [6].
• Clinical Genetic Test: A clinical genetic test offered by Intergen can also be used to diagnose adPEO by detecting mutations in the POLG gene [5].
• Mitochondrial DNA analysis: This test can be used to identify multiple mitochondrial DNA deletions, which are characteristic of adPEO [8].

It's worth noting that a diagnosis of adPEO is typically established in a proband (an individual with the condition) by identification of a heterozygous pathogenic variant in POLG by molecular genetic testing [11]. A diagnostic team for adPEO may include specialists such as neurologists, ophthalmologists, and genetic counselors.

References: [5] Clinical Genetic Test offered by Intergen for conditions (1): Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4; [6] Test Method: Exome Sequencing with CNV Detection. New York State Approved Test. [8] Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 is characterized by multiple mitochondrial DNA deletions in skeletal ... [9] by A Suomalainen · 1997 · Cited by 173 — Autosomal dominant progressive external ophthalmoplegia (adPEO) is a mitochondrial disease characterized by accumulation of multiple large deletions of mtDNA ... [11] The diagnosis of autosomal dominant progressive external ophthalmoplegia (adPEO) is established in a proband by identification of a heterozygous ...

Autosomal dominant progressive external ophthalmoplegia (adPEO) is a rare genetic disorder that affects the muscles controlling eye movement, leading to progressive ptosis and impaired mobility of the eyes. When considering the differential diagnosis for adPEO, several conditions should be taken into account.

• Mitochondrial myopathies: These are a group of disorders caused by mutations in mitochondrial DNA, which can lead to oxidative phosphorylation defects. Kearns-Sayre syndrome is one such condition that overlaps with adPEO and involves similar symptoms [4][5].
• Chronic progressive external ophthalmoplegia (CPEO): This is an acquired form of strabismus associated with a mitochondrial myopathy, which can be inherited in an autosomal dominant or recessive pattern. CPEO may also involve oxidative phosphorylation defects and should be considered in the differential diagnosis [3].
• Myotonic dystrophy: This is a genetic disorder characterized by muscle stiffness and wasting, as well as other systemic symptoms. Muscle biopsies of patients with myotonic dystrophy can exhibit internal nuclei, ring fibers, sarcoplasmic masses, and early type I fiber atrophy, which may be similar to those seen in adPEO [2].
• Other mitochondrial disorders: Mutations in numerous nuclear-encoded genes can cause autosomal dominant progressive external ophthalmoplegia, both the pure and plus forms. Large-scale mtDNA deletions are also associated with this condition and should be considered in the differential diagnosis [15].

It's essential to note that genetic testing may be invaluable in determining prognosis and additional studies for patients suspected of having adPEO or related conditions.

References: [1] The first sign of progressive external ophthalmoplegia is typically drooping eyelids (ptosis), which can affect one or both eyelids. As ptosis worsens, affected individuals may experience impaired mobility of the eyes [3][5]. [2] Muscle biopsies of patients with myotonic dystrophy exhibits internal nuclei, ring fibers, sarcoplasmic masses, and early type I fiber atrophy [2]. [3] Chronic progressive external ophthalmoplegia is an acquired form of strabismus that may be associated with a mitochondrial myopathy and may be inherited in an autosomal dominant or recessive pattern [3]. [4] Kearns-Sayre syndrome is one such condition that overlaps with adPEO and involves similar symptoms [4][5]. [15] Mutations in numerous nuclear-encoded genes cause autosomal dominant progressive external ophthalmoplegia, both the pure and plus forms. Large-scale mtDNA deletion was 1.5 whereas the prevalence of autosomal dominant progressive external ... external ophthalmoplegia and need to be considered in the differential diagnosis of mitochondrial chronic [15].