Cornelia de Lange syndrome 2

Cornelia de Lange syndrome 2 is an X-linked condition that affects multiple body systems, with a particular impact on cardiac and neurological development. It is caused by mutations in the SMC1A gene, which plays an important role in chromosome cohesion and gene regulation. Although individuals with this condition generally exhibit a milder form of the syndrome compared to other genetic causes, they may experience a range of symptoms, including heart-related issues and seizures. As precise birth prevalence data is not available, the condition is understood to be uncommon.

The clinical presentation of Cornelia de Lange syndrome 2 includes features affecting both the heart and the brain. Some affected individuals develop hypertrophic cardiomyopathy, while seizures are reported in a subset of cases. In addition, many children may experience developmental and intellectual challenges, and the condition has been associated with cognitive and neurological involvement. That not all individuals experience all features, and severity varies considerably.

Cornelia de Lange syndrome 2 results from mutations in the SMC1A gene. The SMC1A gene encodes a protein that is a critical component of the cohesin complex, which is essential for maintaining proper chromosomal structure and regulating gene expression. This condition follows an X-linked dominant pattern, meaning that most cases arise from de novo pathogenic variants, so there is usually no prior family history. Female individuals are primarily affected, although due to variable X-inactivation their symptoms may vary, and affected individuals can pass the pathogenic variant to their offspring. Genetic counseling is recommended to discuss family planning and recurrence risk.

Currently, management focuses on supportive care and symptom relief, as there are no approved treatments specifically for Cornelia de Lange syndrome 2. Treatment is tailored to the individual and typically involves a multidisciplinary team to address both cardiac concerns and neurological development. Regular surveillance is an essential part of long-term care, helping to identify potential complications early. Patients should discuss treatment options with their healthcare team to determine which therapies and supportive services may be most appropriate for their situation, and genetic counseling is recommended for all affected families.

The course of Cornelia de Lange syndrome 2 is highly variable, with outcomes that depend on the severity of symptoms, age at diagnosis, and access to specialized care. With current standards of care, many individuals live into adulthood and experience periods of relative stability after early challenges. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists experienced in managing this condition, and genetic counseling is recommended to explore family planning options.

There is one active clinical trial exploring new treatment approaches for Cornelia de Lange syndrome 2. Clinical trials are underway investigating novel interventions, and individuals interested in these research opportunities can search ClinicalTrials.gov or consult their care team about eligibility.