inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1

Inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1 is a rare inherited disorder caused by harmful changes in the VCP gene, which normally helps cells recycle proteins. The condition can weaken the muscles around the hips and shoulders, thicken or weaken certain bones, and lead to changes in thinking and behavior known as frontotemporal dementia. Although precise numbers are not available, the disorder is considered uncommon. Symptoms most often begin in adulthood and can slowly involve the heart or lungs. The severity and specific features can vary considerably from person to person, so care plans are tailored to each individual.

IBMPFD1 most often comes to medical attention because of slowly progressive weakness of the muscles around the hips and shoulders. Over time this limb-girdle pattern can spread to other muscle groups, leading to generalized muscle wasting, difficulty climbing stairs, rising from a chair, or lifting objects overhead. Some individuals eventually lose the ability to walk without assistance. Bone involvement is characterized by early-onset Paget disease, a condition that causes bone pain, deformity, and an increased risk of fractures. About half of affected adults develop Paget-related bone changes, most commonly in the spine, pelvis, or long bones. Neurological features may include frontotemporal dementia, which can manifest as changes in behavior, language (aphasia), or personality. Roughly one-third of individuals develop cognitive symptoms, and brain imaging may show areas of atrophy. Facial weakness or mild facial palsy is less common but reported. As the disease advances, weakness of respiratory or cardiac muscle can occur, contributing to breathing difficulties or heart problems. Laboratory tests often reveal moderately elevated creatine kinase levels, and muscle biopsy may show rimmed vacuoles, a characteristic microscopic finding. Not all individuals experience all features, and severity varies considerably from person to person.

IBMPFD1 is caused by pathogenic variants in the VCP gene. The VCP protein helps cells break down and recycle other proteins; when it does not function properly, toxic protein aggregates can build up in muscle, bone, and brain cells, leading to the multisystem features seen in this disorder. The condition is inherited in an autosomal dominant pattern. This means one altered copy of the VCP gene is sufficient to cause symptoms, and each child of an affected individual has a 50 percent chance of inheriting the variant. Even within the same family, the specific symptoms and their severity can differ markedly (variable expressivity). Genetic counseling is recommended for individuals with IBMPFD1 and their relatives who are considering family planning.

Currently, management focuses on supportive care tailored to each person’s specific symptoms. Physical and occupational therapy can help maintain mobility and delay loss of function, while assistive devices such as braces, walkers, or wheelchairs promote independence. Standard medical treatments for Paget disease of bone or frontotemporal dementia may be used as recommended by the appropriate specialists. Respiratory and cardiac evaluation is important because weakness of these muscle groups can develop. Long-term management includes regular surveillance for potential complications. Suggested monitoring may include periodic assessment of muscle strength and respiratory function, bone imaging to track Paget activity, and cognitive evaluations. Because needs often span neurology, orthopedics, cardiology, pulmonology, and rehabilitation medicine, care is best coordinated by a multidisciplinary team. Genetic counseling offers guidance on inheritance, family testing, and reproductive options. At present no therapies are specifically approved to modify the underlying disease process, but individuals should discuss emerging options and symptomatic treatments with their healthcare team.

The course of IBMPFD1 is progressive but highly variable. Some individuals maintain independent ambulation and minimal cognitive changes for many years, while others experience more rapid muscle decline, bone complications, or dementia. Respiratory or cardiac involvement can contribute to serious health issues in later stages. Outcomes described in medical literature continue to evolve as standards of care improve. Early recognition of symptoms, proactive monitoring, and timely interventions for bone, muscle, or respiratory complications can positively influence quality of life. Families often find it helpful to connect with neuromuscular or neurogenetic specialists familiar with this condition, and enrolling in disease registries can help researchers better understand long-term outcomes and support the development of new therapies.

Clinical trials are underway exploring new treatment approaches for IBMPFD1. Individuals interested in participating can search ClinicalTrials.gov or consult their care team about eligibility.