aneurysm-osteoarthritis syndrome

Aneurysm-osteoarthritis syndrome is a multi-system condition that primarily affects the vascular and musculoskeletal systems. It is caused by pathogenic variants in the SMAD3 gene, which plays a role in the transforming growth factor-beta signaling pathway. Inherited in an autosomal dominant pattern, the syndrome can be observed in individuals across different ages, with clinical manifestations emerging as complications arise. Because the condition is very rare, it affects fewer than one in a million people.

The clinical features of aneurysm-osteoarthritis syndrome reflect its involvement of multiple organ systems. Vascular manifestations include problems such as ascending aortic dissection, thoracic aortic aneurysm, arterial tortuosity, and tortuous cerebral arteries, while individuals may also present with varicose veins. Musculoskeletal issues are prominent, with intervertebral disk degeneration, osteoarthritis, osteopenia, spondylolisthesis, arachnodactyly, pes planus, osteochondritis dissecans, and protrusio acetabuli being reported. Additional features such as a high palate, dental malocclusion, various types of hernias, soft skin, bruising susceptibility, chronic fatigue, and migraine may also occur. Not all individuals experience all features, and severity varies considerably.

Aneurysm-osteoarthritis syndrome is caused by pathogenic variants in the SMAD3 gene, which is important for proper signaling in the transforming growth factor-beta pathway. This condition is inherited in an autosomal dominant manner, meaning that a single copy of the altered gene can contribute to the development of the condition. It is also characterized by variable expressivity, with the range and severity of symptoms differing even among affected family members, and not all individuals who inherit the variant will manifest every feature.

Currently, management of aneurysm-osteoarthritis syndrome focuses on supportive care and symptom management, as no specific FDA-approved or foundational therapies are available for this condition. Treatment is individualized and typically involves a multidisciplinary team approach that may include cardiology, orthopedics, and genetic counseling, with regular surveillance to monitor for vascular and skeletal complications. Patients are encouraged to discuss treatment options with their healthcare providers to determine the most appropriate strategies for their situation.

The long-term outlook for individuals with aneurysm-osteoarthritis syndrome varies widely depending on the severity and combination of symptoms. Some individuals may experience progression in vascular or musculoskeletal features, while others might have periods of relative stability. With modern standards of care and proactive monitoring, many individuals are able to manage their symptoms effectively. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to seek genetic counseling and connect with specialists to discuss ongoing management and support options.