prenatal-onset spinal muscular atrophy with congenital bone fractures

Prenatal-onset spinal muscular atrophy with congenital bone fractures is a severe condition that affects both the neuromuscular system and the skeletal system. It is associated with changes in the ASCC1 and TRIP4 genes, which play roles in muscle and bone development. Although the exact inheritance pattern has not been established, this condition is extremely rare, affecting fewer than 1 in 1,000,000 people. Early signs may be evident even before birth, and the presentation can be highly variable.

The clinical presentation of this condition involves a combination of muscle weakness and bone fragility, with congenital fractures potentially being a key feature. Infants may present with challenges related to movement and muscle tone, and the skeletal vulnerabilities can lead to fractures at or shortly after birth. Not all individuals experience all features, and severity varies considerably. Given the rarity of the condition, detailed symptom profiles are still being defined as more cases are identified and studied.

This condition is linked to variants in the ASCC1 and TRIP4 genes, both of which are important for proper muscle and bone development. The exact mechanism by which alterations in these genes lead to the clinical features is still under investigation, and no specific inheritance pattern has been described in the current data. Families are encouraged to seek genetic counseling to better understand the potential implications for family planning and to discuss any concerns regarding genetic contributions.

Management of prenatal-onset spinal muscular atrophy with congenital bone fractures involves a multidisciplinary approach. Although no foundational therapies specific to this condition were provided, supportive care is central to managing symptoms and may include physical therapy, respiratory support, and other interventions tailored to individual needs. In addition, FDA-approved treatments such as SPINRAZA (nusinersen) and EVRYSDI (risdiplam) are available to address aspects of the neuromuscular symptoms, and the FDA-approved gene therapy Zolgensma (onasemnogene abeparvovec-xioi) offers a treatment option for eligible patients. Patients and families are advised to discuss treatment options with their healthcare team to determine the most appropriate strategy and to consider genetic counseling as part of comprehensive care.

The long-term outlook for individuals with this condition is variable, with outcomes depending on the severity of neuromuscular and skeletal involvement as well as access to specialized care. With current standards of care, many individuals can experience periods of stabilization, and advances in treatment have improved overall outcomes over recent decades. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with specialist teams and genetic counselors to gain a clear understanding of potential outcomes and appropriate next steps for ongoing management.