Ichthyosis is normally caused by changes in the genes we inherit from our parents, but can also develop later in life. These changes in our genes are known as mutations (also known as variants), and they change the way that the skin develops and lead to excess of skin growth. We know many of the changes in our genes which lead to the various types of ichthyosis and this allows us to diagnose the condition early on.

Inheritance patterns in ichthyosis can be either dominant, recessive or X-linked. This means that depending on the type of ichthyosis you have, there are different percentage chances that the condition will be inherited.

What is Prenatal Testing?

Prenatal testing is a method that can be used during pregnancy to identify if the unborn baby has ichthyosis. If parents have a child with ichthyosis, genetic testing is performed to find out which gene variant has caused the ichthyosis. Prenatal testing can then be used to identify if the unborn child has the variant which causes ichthyosis in this family.

Types of Prenatal Testing

• Chorionic Villus Sampling (CVS): 11-13 weeks. In CVS a needle is used to take a piece of the placenta, which has the same genetic information as the unborn baby. This placenta is then tested to see if the genetic variant causing ichthyosis is present.
• Amniocentesis: 15-18 weeks. In Amniocentesis a needle is used to take a small amount of amniotic fluid, which has some of the unborn baby’s genetic material. This fluid can then be tested to see if the unborn baby has the gene variant causing ichthyosis.
• Non-Invasive Prenatal Diagnosis (NIPD): NIPD is a blood test which can examine foetal DNA in the mother's blood. A special assay has to be developed. This has been developed in the NHS for some rare inherited disorders eg cystic fibrosis and some forms of muscular dystrophy, but is not yet available for ichthyosis.
• Pre-implantation Genetic Diagnosis (now also known as preimplantation genetic testing for monogenic disorders [PGT-M]): This method involves in vitro fertilisation (IVF). Eggs from mother and sperm from father are combined in the laboratory and then embryos can be tested for the gene variant causing ichthyosis and only embryos without the variant are implanted into the womb.

Considerations

Benefits:

• Early Detection: Prenatal testing allows you to test and thus identify ichthyosis early. This can help you make informed decisions about pregnancy.
• Preparation: It may be helpful for you to know what to expect before your child is born. Ichthyosis is associated with challenges and preparing yourself can help face these.

Challenges:

• Procedural Complication Risks: CVS and amniocentesis are both invasive tests, and there is a small risk of miscarriage or complications such as infection and damage from the needle
• Treatment Options: While prenatal testing can provide early diagnosis, treatment options for ichthyosis are often focused on managing symptoms rather than a cure.
• Funding: Prenatal testing will require a consultation with a clinical geneticist and a genetics counsellor and then approval for prenatal testing.

Factors to Consider when making a decision:

• Information: Make sure you have gathered information on ichthyosis including the types which can be tested for and the treatment options available. Remember there may be new treatments on the horizon. Also make sure you have sought information on the prenatal testing process where you live, including waiting lists and funding, and what your options are after testing.
• Currently approved by Human Fertilisation & Embryology Authority: Ichthyosis (X-linked, XLI), Harlequin ichthyosis, Ichthyosis follicularis-alopecia-photophobia Syndrome; IFAP Syndrome 1 With or Without Bresheck Syndrome; (IFAP1), Ichthyosis with confetti, Ichthyosis, cyclic, with epidermolytic hyperkeratosis (ICEHK), Ichythosis hystrix of Curth-Macklin.
• Professional Consultations: A consultation with a genetic counsellor can be a useful source of further information. Here you can discuss benefits and risks of prenatal diagnosis, and ask any questions you might have.
• Personal: Prenatal diagnosis is a personal decision which depends on your values, beliefs and personal choice! It can be helpful to involve family and friends for support, but remember the decision is yours. If you have a partner, make sure to discuss the options with them.
• Conclusion

Decisions about Prenatal testing for ichthyosis are very personal and there are many things to consider. It can be helpful to discuss your options with people close to you, professionals or those with prior experience. Support groups can be a useful source of meeting people with experience and in similar situations. There is no right or wrong answer and it is important to understand the risks, benefits and possible outcomes when making a decision that aligns with your personal values and preferences.

Please seek guidance from healthcare providers or genetic counsellors for further guidance.

Charlotte is an aspiring Dermatologist who is currently undertaking an MRes in Human Tissue Repair at University College London and works as a doctor at University College London Hospital in London. She completed her undergraduate medical studies at University of Cambridge, Trinity College where she intercalated with a BA in Genetics.

Dr Charlotte Muehlschlegel, University College London Hospital, MB BChir, BA, MA (Hons)

An ISG member with Ichthyosis en Confetti recently shared her story of undergoing the journey with PGT which you can read here.

Using cutting-edge genetic testing services like PGT (Preimplantation Genetic Testing), via services available in Devon with Fertility Exeter and Royal Devon University Healthcare NHS Foundation Trust Georgina has been able to have two healthy children.