Is Kabuki syndrome hereditary?

Is Kabuki syndrome hereditary?

Kabuki syndrome is a rare genetic disorder that affects multiple parts of the body. It is characterized by distinct facial features, developmental delays, and various other health issues. Many individuals diagnosed with Kabuki syndrome have parents who do not have the condition, leading to the question of whether it is hereditary.

Genetic Basis of Kabuki Syndrome

Kabuki syndrome is primarily caused by mutations in two specific genes: KMT2D (also known as MLL2) and KDM6A. These genes provide instructions for producing proteins that are involved in regulating gene activity and controlling the development of various tissues and organs in the body.

Spontaneous Mutations

In most cases, the mutations responsible for Kabuki syndrome occur spontaneously during the formation of reproductive cells (eggs or sperm) or early in embryonic development. These mutations are not inherited from the parents and are instead considered de novo mutations. De novo mutations are random events that happen by chance and are not influenced by any specific factors in the parents' genetic makeup or lifestyle.

Recurrence Risk

Since the majority of Kabuki syndrome cases are caused by de novo mutations, the risk of recurrence in siblings is generally low. The chance of having another child with Kabuki syndrome is estimated to be less than 1% for most families. However, it is important to note that the risk may be slightly higher for parents who have a child with Kabuki syndrome due to a mutation in the KMT2D gene.

Autosomal Dominant Inheritance

In a small percentage of cases, Kabuki syndrome can be inherited from an affected parent. This occurs when one of the parents carries a mutation in either the KMT2D or KDM6A gene and passes it on to their child. In these cases, Kabuki syndrome follows an autosomal dominant inheritance pattern.

Autosomal Recessive Inheritance

In rare instances, Kabuki syndrome can also be inherited in an autosomal recessive manner. This means that both parents are carriers of a mutation in the same gene (either KMT2D or KDM6A) but do not have the syndrome themselves. When both parents are carriers, there is a 25% chance with each pregnancy that their child will have Kabuki syndrome.

Genetic Testing and Counseling

Genetic testing can help confirm a diagnosis of Kabuki syndrome and identify the specific gene mutation involved. It can also provide information about the inheritance pattern, which can be crucial for family planning decisions.

For families with a child diagnosed with Kabuki syndrome, genetic counseling is highly recommended. Genetic counselors can explain the inheritance patterns, discuss the risk of recurrence, and provide guidance on family planning options. They can also help parents understand the potential implications of genetic testing for other family members.

Conclusion

In summary, Kabuki syndrome is primarily caused by spontaneous mutations that occur randomly and are not inherited from the parents. However, in a small percentage of cases, the syndrome can be inherited from an affected parent following an autosomal dominant or recessive inheritance pattern. Genetic testing and counseling play a crucial role in understanding the genetic basis of Kabuki syndrome and making informed decisions about family planning.