Kabuki syndrome 2

Kabuki syndrome 2 is an inherited condition that impacts multiple aspects of development, manifesting in distinctive facial features and growth challenges. It is caused by pathogenic variants in the KDM6A gene, which plays a key role in regulating gene expression during early development. The condition follows an X‐linked dominant inheritance pattern, with most cases arising from de novo variants, meaning there is usually no family history. While precise prevalence data are not available, Kabuki syndrome 2 is recognized as a multi-system condition with symptoms evident from early childhood.

Individuals with Kabuki syndrome 2 generally present with a characteristic set of clinical features. Nearly all affected persons exhibit prominent fingertip pads, areolar fullness, postnatal growth retardation, long palpebral fissures, and global developmental delay with associated intellectual disability. Additional common findings include short stature, and many experience macrotia, eversion of the lateral third of the lower eyelids, feeding difficulties in infancy, joint hypermobility, and seizures, among other features. The cognitive and developmental challenges often require early intervention, and families benefit from a multidisciplinary approach to address both physical and neurological aspects. Not all individuals experience all features, and severity varies considerably.

Kabuki syndrome 2 is caused by variants in the KDM6A gene, a gene that is integral to chromatin remodeling and proper regulation of gene expression during development. The condition is inherited in an X‐linked dominant pattern, and most cases arise from de novo pathogenic variants, meaning that there is typically no family history of the condition. Females are most commonly affected, while affected males may experience more severe manifestations. Given these inheritance dynamics, affected individuals who reproduce have a risk of passing on the variant, and families are encouraged to pursue genetic counseling to better understand recurrence risks and reproductive options.

Currently, management of Kabuki syndrome 2 focuses on supportive care and symptom management, as no treatments are specifically approved for this condition. Treatment is highly individualized and typically involves a multidisciplinary team that may include developmental pediatricians, neurologists, and therapists, among others. Interventions such as physical therapy, occupational therapy, and specialized educational support are common to address motor and cognitive challenges. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become more serious. Genetic counseling is also recommended to discuss treatment options and inheritance implications, ensuring that each patient receives care tailored to their specific needs.

Outcomes for individuals with Kabuki syndrome 2 vary widely and depend on the severity of symptoms, timing of diagnosis, and access to supportive care. With current standards of care, many individuals continue to progress and develop skills, although challenges related to intellectual disability and developmental delay remain a lifelong concern. The condition is marked by early developmental challenges that tend to stabilize over time, with variability in physical and cognitive progress between individuals. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to seek guidance from specialists and genetic counselors, as ongoing surveillance and tailored care can help optimize long-term outcomes.

Clinical trials exploring new treatment approaches for Kabuki syndrome 2 are currently underway. Although only a limited number of trials have been identified, this active area of research reflects ongoing efforts to expand therapeutic options. Individuals interested in clinical trials can search ClinicalTrials.gov or consult with their care team regarding potential eligibility for emerging treatments.