Oculopharyngodistal myopathy

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Oculopharyngodistal myopathy (OPDM)

OPDM is a rare genetic disorder that causes slowly worsening muscle weakness. It most often affects the muscles around the eyes, face, throat, and the distal parts of the arms and legs. The condition is usually inherited in an autosomal dominant way, meaning one mutated copy of a gene can cause illness.

What causes OPDM
- OPDM has four known genetic causes, each due to a trinucleotide repeat expansion in a different gene: LRP12, GIPC1, NOTCH2NLC, and RILPL1.
- These mutations lead to a group of related conditions called OPDM1, OPDM2, OPDM3, and OPDM4. Most families have a mutation in one of these genes and inherit the condition from a parent.

Signs and symptoms
- Symptoms typically begin in adulthood.
- Common features: drooping of the eyelids (ptosis) and trouble moving the eyes (ophthalmoplegia); weakness of facial muscles; difficulty swallowing (dysphagia) and slurred speech (dysarthria); weakness and wasting of the muscles in the arms and legs, especially toward the ends (distal muscles).
- Some people may have hearing loss, more severe weakness near the trunk (proximal weakness), or weakness on one side (unilateral) in rare cases.

Complications
- Depending on how severe the weakness is, people may have trouble with daily tasks or doing manual work.

Diagnosis
- A doctor will assess symptoms and family history.
- Genetic testing can confirm OPDM by detecting the repeat expansions in LRP12, GIPC1, NOTCH2NLC, or RILPL1.
- Some tests specifically measure the size of the repeats to help confirm the diagnosis.

Genetics and prevalence
- OPDM is caused by mutations in four different genes and is inherited in an autosomal dominant pattern.
- Worldwide, about 78 families are known to have OPDM, most of them of East Asian descent (Japanese and Chinese people are commonly affected).
- OMIM describes OPDM1, OPDM2, and OPDM3 as subtypes with published family counts; OPDM4 is the fourth genetic form.

History
- OPDM was first described in 1977 as an autosomal dominant myopathy with ptosis and facial/bulbar weakness, plus distal limb involvement beginning around midlife.
- In 2019–2020, researchers identified the four gene repeat expansions (LRP12, GIPC1, NOTCH2NLC, and RILPL1) as causes of OPDM, helping to explain how the condition develops and why it runs in families.