Proximal myotonic dystrophy

Proximal Myotonic Dystrophy (PROMM), also known as Myotonic Dystrophy Type 2 (DM2), is a form of myotonic dystrophy characterized by muscle weakness and myotonia, which is a difficulty in relaxing muscles after they contract. Unlike Myotonic Dystrophy Type 1 (DM1), which is caused by a CTG trinucleotide repeat expansion in the DMPK gene, DM2 is caused by a CCTG tetranucleotide repeat expansion in the CNBP (ZNF9) gene. This genetic disorder is inherited in an autosomal dominant manner, meaning that only one copy of the altered gene is necessary to cause the disorder.

Symptoms

The symptoms of Proximal Myotonic Dystrophy can vary widely among affected individuals and may include muscle weakness, myotonia, cataracts, cardiac abnormalities, endocrine disorders, and cognitive impairments. Muscle weakness in DM2 tends to be more pronounced in the proximal muscles, which are closer to the center of the body, such as the thighs and hips, rather than the distal muscles, which are farther from the center of the body. This proximal muscle weakness can lead to difficulties in performing tasks such as climbing stairs or rising from a seated position.

Genetics

Proximal Myotonic Dystrophy is caused by a mutation in the CNBP gene, which leads to an abnormal expansion of a CCTG tetranucleotide repeat. The length of the repeat expansion can vary greatly among individuals and can influence the severity and onset of the disease symptoms. DM2 is inherited in an autosomal dominant pattern, which means that having just one copy of the mutated gene is enough to cause the disorder.

Diagnosis

The diagnosis of Proximal Myotonic Dystrophy is primarily based on clinical evaluation and the presence of characteristic symptoms. Molecular genetic testing can confirm the diagnosis by identifying the CCTG repeat expansion in the CNBP gene. Electromyography (EMG) and muscle biopsy may also be used to support the diagnosis.

Treatment

There is currently no cure for Proximal Myotonic Dystrophy, and treatment focuses on managing symptoms and improving quality of life. This may include physical therapy to maintain muscle strength and mobility, medications to manage myotonia and cardiac symptoms, and regular monitoring for potential complications such as cataracts and endocrine disorders.

Prognosis

The prognosis for individuals with Proximal Myotonic Dystrophy can vary widely depending on the severity of symptoms and the presence of complications. While the disorder is progressive, most individuals maintain a good quality of life with appropriate management of symptoms.