Kabuki syndrome 1

Kabuki syndrome 1 is a multisystem disorder that involves a range of craniofacial, skeletal, renal, and neurological features. It is caused by pathogenic variants in the KMT2D gene, which plays a key role in regulating gene expression during development. The condition is inherited in an autosomal dominant pattern and typically presents in childhood. Precise prevalence estimates are not well established.

Individuals with Kabuki syndrome 1 exhibit a distinctive blend of clinical features. Characteristic facial differences include telecanthus, downslanted palpebral fissures, a short nose with anteverted nares, a high narrow palate, and thick or tented lower lip vermilion along with large earlobes. In addition, notable skeletal abnormalities such as brachydactyly, finger clinodactyly, thoracic scoliosis, and retrognathia are evident. Neurological involvement is highlighted by lateral ventricle dilatation and focal impaired awareness seizures, while other features include nasolacrimal duct obstruction, a weak cry, sensorineural hearing impairment, renal issues like ureteropelvic junction obstruction, bilateral renal hypoplasia, renal insufficiency, and even lobar holoprosencephaly. Not all individuals experience every feature, and severity varies considerably.

Kabuki syndrome 1 is caused by pathogenic variants in the KMT2D gene, which is instrumental in regulating gene expression during development. The condition is inherited in an autosomal dominant manner, meaning that a single altered copy of the gene can lead to the disorder and each child of an affected individual has a 50% chance of inheriting the variant. It is important to understand that not every individual with a variant will display all symptoms, as there is notable variable expressivity.

Currently, management focuses on supportive care and symptom management, with treatment tailored to the individual. A multidisciplinary team is integral to addressing the various aspects of the condition, and long-term surveillance is an essential part of care to detect and manage complications such as hearing loss, renal dysfunction, and skeletal issues. Patients should discuss treatment options with their healthcare team to determine the most appropriate strategies for their particular situation, and genetic counseling is recommended to help families understand the inheritance pattern and implications for family planning.

Kabuki syndrome 1 is a lifelong condition with a highly variable course that depends on the severity of symptoms, age at diagnosis, and access to comprehensive care. With current standards of care, many individuals experience improvements in quality of life, although some complications may require ongoing management. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition for additional guidance and support.

Clinical trials are currently underway exploring new treatment approaches for Kabuki syndrome 1. Individuals interested in learning more about experimental therapies can search ClinicalTrials.gov or consult their care team about eligibility for ongoing trials.