Oculopharyngeal Muscular Dystrophy (OPMD)

Diagnosis

The clinical features of oculopharyngeal muscular dystrophy (OPMD) overlap with features of several other neuromuscular diseases, making diagnosis a challenge. A doctor may begin to suspect an OPMD diagnosis based upon clinical evaluation, a detailed patient history, and identification of characteristic findings, such as droopy eyelids (ptosis), difficulty swallowing (dysphagia), and difficulty speaking (dysarthria).¹

A diagnosis of OPMD can be confirmed through commercially available blood tests that detect the specific genetic abnormality in the PABPN1 gene, known as a repeat expansion, that is associated with OPMD. The PABPN1 gene normally contains 10 repeats of a particular DNA sequence (GCN), but the mutated versions of the PABPN1 gene that cause OPMD contain an expanded number (11-18) of GCN repeats.² The blood tests used to confirm an OPMD diagnosis detect the expanded numbers of GCN repeats in the mutated PABPN1 gene.

Sometimes, an individual with suspected OPMD is found to have two normal copies of the PABPN1 gene. In this case, muscle biopsy may be used to detect the subtle histological features of OPMD.¹ Because the PABPN1 gene serves as a blueprint for the PABPN1 protein, mutations in the PABPN1 gene lead to the formation of abnormal PABPN1 proteins that form clumps in muscle cells (intranuclear inclusions or INI).³ These clumps accumulate and are thought to impair the normal functioning of muscle cells, and possibly nerve cells as well. INI are highly specific to OPMD; other common biopsy findings in patients with OPMD that are less specific include variation in the diameter and appearance of muscle fibers, ragged red fibers, and rimmed vacuoles.^1,4 Therefore, presence of these features in a muscle biopsy is generally used in concert with other factors to help confirm an OPMD diagnosis.

For more on the genetic causes of OPMD, see Causes/Inheritance.

For more on the genetics of neuromuscular disease in general, see Facts About Genetics and Neuromuscular Diseases.

To learn more about getting a definitive genetic diagnosis, see The Importance of Genetic Testing.

References

1. Trollet C, Gidaro T, Klein P, et al. Oculopharyngeal Muscular Dystrophy. 2001 Mar 8 [Updated 2014 Feb 20]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle: University of Washington, Seattle; 1993-2020.
2. Richard P, Trollet C, Stojkovic T, et al. Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy. Neurology. 2017;88(4):359-365. doi:10.1212/WNL.0000000000003554
3. Calado A, Tomé FMS, Brais B, et al. Nuclear inclusions in oculopharyngeal muscular dystrophy consist of poly(A) binding protein 2 aggregates which sequester poly(A) RNA. Hum Mol Genet. 2000. doi:10.1093/oxfordjournals.hmg.a018924
4. Gidaro T, Negroni E, Perié S, et al. Atrophy, fibrosis, and increased PAX7-positive cells in pharyngeal muscles of oculopharyngeal muscular dystrophy patients. J Neuropathol Exp Neurol. 2013. doi:10.1097/NEN.0b013e3182854c07