autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)

Autosomal dominant limb-girdle muscular dystrophy type 1D (LGMD1D) is a condition that primarily affects the muscles around the pelvic girdle, with patients typically experiencing slowly progressive weakness that begins in adulthood. It is caused by heterozygous missense mutations in the DNAJB6 gene, with the disorder following an autosomal dominant inheritance pattern. Individuals with this condition commonly present with proximal muscle weakness and gait abnormalities while generally having minimal or no involvement of the shoulder girdle, cardiac, or respiratory systems. The condition is very rare, affecting fewer than 1 in 1,000,000 people.

Characteristic findings in LGMD1D include the consistent presence of rimmed vacuoles and decreased compound muscle action potential amplitude. Early in the disease course, individuals may notice a waddling gait and difficulty climbing stairs, while generalized muscle weakness is a principal feature observed in most cases. As the condition progresses, some patients can experience loss of ambulation, dysarthria, and other variable features such as increased variability in muscle fiber diameter and challenges with running. Not all individuals experience all features, and severity varies considerably.

LGMD1D is caused by heterozygous missense mutations in the DNAJB6 gene. The condition is inherited in an autosomal dominant manner, meaning that a single copy of the altered gene inherited from an affected parent is sufficient to result in the disorder. Even within affected families, the specific symptoms and their severity can vary considerably, which is an example of variable expressivity. Genetic counseling is recommended to help families understand the inheritance pattern and discuss family planning options.

Currently, management for LGMD1D focuses on supportive care and symptom management, with treatment being tailored to each individual. Although there are no FDA-approved or foundational therapies specifically for this condition, a multidisciplinary approach, including physical therapy, occupational therapy, and regular surveillance, is essential to maintain muscle function and manage complications. Patients are encouraged to discuss treatment options with their healthcare team and to seek genetic counseling for further guidance.

The course of LGMD1D is generally one of slowly progressive muscle weakness primarily affecting the pelvic girdle, although the severity and rate of progression vary widely among individuals. With current standards of care and a multidisciplinary approach, many individuals are able to maintain a good quality of life well into adulthood. Outcomes described in medical literature continue to evolve as standards of care improve, and regular surveillance helps in the early identification of emerging symptoms. Families often find it helpful to connect with specialists familiar with this condition, and genetic counseling can provide further guidance on long-term management.

There are a few clinical trials currently underway exploring new treatment approaches for LGMD1D. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.