Lesch Nyhan syndrome

Lesch Nyhan syndrome is inherited in an X-linked recessive manner.^[1] A condition is X-linked if the changed (mutated) gene responsible for the condition is located on the X chromosome. The X chromosome is one of the two sex chromosomes; females have two X chromosomes, and males have one X and one Y chromosome. Females who have one mutated copy of the responsible gene (on one of their X chromosomes) usually do not have the condition and are referred to as carriers. This is because they still have a working copy of the responsible gene on their other X chromosome. Males with one mutated copy of the responsible gene have signs and symptoms of the condition (they are affected) because they do not have another X chromosome with a working copy of the gene. This is why X-linked recessive disorders, including Lesch Nyhan syndrome, occur much more frequently in males.

Lesch Nyhan syndrome is caused by mutations in the HPRT1 gene. A female who is a carrier of Lesch Nyhan syndrome has a 50% chance of passing on the mutated HPRT1 gene in each pregnancy. This is because a carrier female will randomly pass on one of her X chromosome to each child. Sons who inherit the mutated gene will be affected, and daughters who inherit the mutated gene will be carriers. This means that with each pregnancy, a female who is a carrier has a:

• 50% (1 in 2) chance of having an unaffected son or daughter
• 25% (1 in 4) chance of having an affected son
• 25% chance of having a carrier daughter^[1]

With advanced planning and appropriate testing, it may be possible for a carrier to prevent having a child with Lesch Nyhan syndrome. Depending on each person's individual situation and choices, this may be accomplished either during a pregnancy, or before a pregnancy begins.

To find out whether a fetus is affected during a pregnancy, prenatal testing can be performed either by molecular genetic testing or biochemical genetic testing. Molecular genetic testing may be done if the specific mutation in the HPRT1 gene has been identified in the family. The usual procedure is to first determine fetal sex by performing chromosome analysis on fetal cells obtained by chorionic villus sampling (at about 10 to 12 weeks gestation), or by amniocentesis (usually performed at about 15 to 18 weeks gestation). If the fetus is known to be male, DNA from fetal cells can then be tested for the mutation in the family. If the specific mutation in the HPRT1 gene in the family is not known, biochemical genetic testing is preferred. This testing also requires either chorionic villus sampling or amniocentesis, but involves measuring HPRT enzyme activity in the cells obtained during the procedure. If Lesch Nyhan syndrome is confirmed in the fetus by either method of testing, pregnancy options including pregnancy termination may be discussed with a health care provider.

As an alternative to prenatal diagnosis during the pregnancy, preimplantation genetic diagnosis (PGD) before a pregnancy may be available if the mutation in the family is known. PGD is done after in vitro fertilization (IVF) to diagnose a genetic condition in an embryo before it is introduced into the uterus. When having PGD, only embryos known to be unaffected are introduced into the uterus for a possible pregnancy.

People interested in genetic testing, prenatal diagnosis, and/or preimplantation genetic diagnosis should speak with a genetics professional.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.