SNP Shot: Genomic Insights

Kabuki syndrome is a multi-system disorder affecting various parts of the body. It is recognized by distinct facial features, including prominent, arched eyebrows; long eyelashes; elongated eyelid openings (palpebral fissures) with the lower eyelids turned outward (eversion) at the outer corners; a flattened and broadened nasal tip; and large, noticeable earlobes. The syndrome's name is derived from the similarity of these facial characteristics to the makeup worn in traditional Japanese Kabuki theater performances.

Individuals with Kabuki syndrome may experience developmental delays and intellectual disabilities, ranging from mild to severe. Seizures, an abnormally small head circumference (microcephaly), or reduced muscle tone (hypotonia) may also be present. Some affected individuals have eye-related issues such as rapid, uncontrolled eye movements (nystagmus) or misaligned eyes (strabismus).

Additional common features of Kabuki syndrome include short stature and skeletal irregularities like scoliosis (an abnormal sideways curvature of the spine), short pinky fingers, or hip and knee joint problems. Oral abnormalities can include a cleft palate (an opening in the roof of the mouth) or a high-arched palate. Dental problems are also frequently observed. Furthermore, people with Kabuki syndrome might exhibit unusual fingerprint patterns and fleshy pads on their fingertips, known as fetal finger pads. These pads are typically present in developing fetuses but usually disappear before birth.

A diverse range of other health concerns can occur in some individuals with Kabuki syndrome. Frequently reported issues include heart defects, recurrent ear infections (otitis media), hearing impairment, and the onset of puberty at an early age.

Inheritance:

Kabuki syndrome caused by variations in the KMT2D gene follows an autosomal dominant inheritance pattern. This means that having just one altered copy of the gene in each cell is enough to cause the condition. When Kabuki syndrome is caused by changes in the KDM6A gene, it shows X-linked dominant inheritance. The KDM6A gene is found on the X chromosome, one of the two sex chromosomes. In females (with two X chromosomes), one altered copy in each cell can lead to the disorder. In males (with only one X chromosome), a change in their single copy will cause the disorder. A hallmark of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Most cases of Kabuki syndrome arise from a new genetic change in either the KMT2D or KDM6A gene, occurring in individuals with no family history of the condition. In a minority of cases, an affected person is thought to have inherited the altered gene from a parent who also has Kabuki syndrome.