congenital heart defects and skeletal malformations syndrome

Congenital heart defects and skeletal malformations syndrome is a multi-system condition characterized by abnormalities affecting the heart and the skeletal system, along with distinctive facial features and growth challenges. Genetic variants in the ABL1 gene are associated with this syndrome, which is inherited in an autosomal dominant manner. It is typically recognized in infancy or early childhood due to early presenting features such as failure to thrive and heart defects. The condition is very rare, affecting fewer than 1 in 1 million people, and not all individuals experience all features, with severity varying considerably.

Individuals with this syndrome frequently present with a range of clinical features affecting several organ systems. Cardiac anomalies, including atrial septal defects, ventricular septal defects, and aortic root aneurysms, are common, while skeletal malformations such as scoliosis, pectus excavatum, joint hypermobility, and short stature contribute to the syndrome’s name. Many affected children experience failure to thrive and global developmental delay, reflecting the cognitive and developmental impact of the condition. Additional features include dental crowding, a high palate, soft skin, cutis marmorata, and distinct facial characteristics like a thin vermilion border and a short chin. Not all individuals experience all features, and severity varies considerably.

The underlying cause of this syndrome is linked to variants in the ABL1 gene, which plays a key role in cellular signaling and function. It is inherited in an autosomal dominant pattern, meaning that a single altered copy of the gene can result in the condition. This inheritance pattern implies that an affected individual has a 50% chance of passing the variant to each child. Even within the same family, the severity and specific symptoms can vary considerably, illustrating the concept of variable expressivity.

Currently, management focuses on supportive care and symptom management, with treatment plans tailored to the individual’s needs. Although there are no specific foundational therapies or FDA-approved treatments for this condition, care typically involves a multidisciplinary team to address cardiac, skeletal, and developmental issues. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Patients are advised to discuss treatment options and appropriate follow-up with their healthcare team, and genetic counseling is recommended to provide guidance on family planning.

Outcomes for individuals with congenital heart defects and skeletal malformations syndrome vary widely, depending on the severity of the cardiac and skeletal anomalies and the level of access to specialized care. With current standards of care, many affected individuals manage their symptoms effectively, although some may face ongoing challenges that require coordinated medical support. Outcomes described in medical literature continue to evolve as standards of care improve, and families often find it helpful to connect with specialists familiar with this condition for ongoing support and guidance.