Harlequin Ichthyosis: Causes, Symptoms & Treatments

Medically Reviewed by Zilpah Sheikh, MD on December 18, 2023
Written by Rebekah Kuschmider, Nechama F. Sammet Moring
20 min read

Harlequin ichthyosis is the most severe type of ichthyosis, a family of skin conditions in which skin cells turn over too slowly or too quickly. The result is dry, scaly skin. Some kinds of ichthyosis are minor, and you can treat them with a careful skin care routine. Others, like harlequin ichthyosis, are more serious and require significant medical care. Most types of ichthyosis are genetic, and they are lifelong conditions.

A so-called “harlequin fetus” will have symptoms of this rare condition before birth. Babies with harlequin ichthyosis are born with tight, scaled skin all over their bodies. The condition is life-threatening, though improved treatment means that some people with harlequin ichthyosis can live to adulthood.

Experts estimate that harlequin ichthyosis affects one in 500,000 live births. Every year, fewer than 1 babies in the U.S. are born with harlequin ichthyosis.

Ichthyosis is a group of related genetic conditions that impact how your body makes and sheds skin cells. Harlequin ichthyosis is the most severe kind of ichthyosis that you can have, and it is very rare.

Doctors now sort the different kinds of ichthyosis by whether you inherit the genes for it from one or both parents. Harlequin ichthyosis is part of a group called autosomal recessive congenital ichthyosis (ARCI). Other types of ichthyosis in this group are lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). 

Babies with LI and CIE are often born with a clear membrane called a collodion covering their bodies. Like babies with harlequin ichthyosis, they might have tight skin on their face that pulls their lips or eyelids back. People with LI often have issues with the skin around their eyes, which can lead to eye irritation and vision problems. With CIE, your body replaces certain layers of skin cells too quickly, leading to thicker than usual skin, redness, and flakiness.

Other kinds of ichthyosis include:

  • Ichthyosis vulgaris is the most common kind of ichthyosis, and about 1 in 250-300 people have it. With this kind of ichthyosis, skin cells shed more slowly than usual, and build up on the surface of your skin. Because it can seem like you just have dry skin, many people with ichthyosis vulgaris don’t tell their doctors about it or get diagnosed. It’s treated with moisturizers.
  • Epidermolytic ichthyosis causes the outer layer of skin to blister and peel. Babies with this condition are often born with blisters. People with this kind of ichthyosis usually have redder skin than other people in their family and are more likely to get infections. Because your skin helps your body stay at the right temperature, people with epidermolytic ichthyosis can be very sensitive to hot and cold weather.
  • X-linked ichthyosis only affects people who are assigned male at birth. People assigned female at birth can be carriers—this means that they can pass the gene on to their children, but they don’t have any symptoms themselves. People with X-linked ichthyosis generally have scaly patches that are darker than the rest of their skin, especially on the back of their necks.
  • Syndromes that include ichthyosis. A syndrome is a pattern of different issues that affect a person. Some syndromes include ichthyosis. One example is Sjögren-Larsson Syndrome (SLS), where you are missing a chemical you need to break down certain fats. People with SLS often learn skills such as walking and speaking at a slower pace than others, and many have issues with their eyes or vision. Another example, Netherton Syndrome, causes changes to your skin, hair, and immune system. People who have it are more likely to get allergies, asthma, and eczema, along with ichthyosis.

There are many other kinds of ichthyosis. Doctors will do tests, including genetic testing, to figure out which kind of ichthyosis you have.

If you have harlequin ichthyosis, your body sends too many cells to the outer layer of your skin. As these extra cells build up, the skin becomes very thick and breaks up into dry, scaly plates. These plates and scales are the main symptoms of harlequin ichthyosis. It can also lead to other issues, which show up differently as you age.

Symptoms in newborns and infants 

Babies with harlequin ichthyosis are born with a thick casing of hardened skin all over their bodies. The casing cracks, leading to cuts, called fissures, which go all the way through the baby’s skin. These cracks divide their skin into plate-like patches of thickened skin that look like scales or armor. The casing slowly falls off during the first few weeks, and more flexible skin replaces it.

Usually, our skin acts like a wall to keep germs out. For babies with harlequin ichthyosis, the cracks in their skin let germs in, so they are more likely to get infections. They also have more trouble than other babies keeping their body at the right temperature. The neonatal intensive care unit (NICU) staff will check your baby often to make sure they aren’t getting any infections and that they are warm.

Because the casing is often tight around their chest and belly, babies with harlequin ichthyosis are more likely to have trouble breathing. They might need a breathing tube. The tight skin of the casing also pulls back their lips and eyelids, so their mouth and eyes are always open. This causes their eyes and mouth to look very red because you are seeing the inside of their lips and eyelids.

Other symptoms in newborns can include:

  • Prematurity. This is when a baby is born before their due date. Premature babies can have other problems and need special care because they have not finished growing all the way.
  • Trouble breastfeeding or taking a bottle. Tight, pulled-back lips can make it harder for babies to suck and swallow. They might need a feeding tube.
  • Dehydration and imbalances. Cracks in the baby’s skin let water out more easily. Losing water can lead to an imbalance in chemicals in your body, such as salt (sodium) and electrolytes.
  • Dry eyes and eye infections. This happens because the casing pulls their eyes and eyelids back, so their eyes aren’t as protected. NICU staff will moisturize the baby’s eyes with drops. 
  • Curled-up fingers, toes, arms, or legs. The thick casing can pull on the baby’s fingers, toes, and limbs, causing them to get stuck in curled-up positions. They might also have trouble moving these body parts. Their feet or hands might be swollen or smaller than usual.
  • Less blood flow. Sometimes, the casing can slow down blood flow to the baby’s arms, legs, fingers, or toes. It can also cut off blood flow all the way. Without blood, the tissue starts to die. The baby might need special splints or a small surgery to keep their blood flowing well.
  • “Extra” fingers or toes. This is called polydactyly. Doctors don’t know why, but babies with harlequin ichthyosis are more likely to have it.
  • Flattened nose. Babies with harlequin ichthyosis often have flatter noses than other people in their families.
  • Small ears. The ears might also be all the way attached to their head, instead of sticking out, because the casing pulls them so tight.
  • Low levels of vitamin D. Some doctors think that this happens because it’s hard for light to get through the baby’s thicker skin (your body needs light to make vitamin D). Other doctors think this could be a side effect of some of the medications given to babies with harlequin ichthyosis.

Symptoms in older children and adults

As babies get older, their symptoms can change, and new symptoms can develop. Harlequin ichthyosis isn’t as dangerous once the thick casing you’re born with falls off, but it is a serious chronic health condition. The main symptom in older children and adults is red, scaly skin that will always need special care. Other symptoms can include:

  • Slower development. Some people with harlequin ichthyosis develop physical skills such as crawling or walking later than other people their age.
  • Very thick skin on the palms and soles of the feet. Some people who have thickened skin on the bottoms of their feet experience pain when they stand on them, and it can make it harder to learn to walk.
  • Delicate, thin hair. This happens to people with all hair types and can be caused by scaly patches on the scalp. 
  • Problems with hearing. Skin flakes or scales can build up in your ears, and the condition may affect your hearing.
  • Joint problems. Some doctors think that people with harlequin ichthyosis are more likely to get arthritis and other problems with their joints. They might also have trouble walking or moving certain parts of their bodies.
  • Shortness. People with harlequin ichthyosis can be shorter and smaller than other people in their families.
  • Sensitivity to heat and cold. Extreme temperatures might bother you more.
  • Trouble sweating. Sweat glands are located in the outer layer of your skin. They might work differently or not at all if you have harlequin ichthyosis. This can make you overheat more easily.
  • Infections. People with harlequin ichthyosis can easily get skin and other infections.
  • Itchiness. About half of people with harlequin ichthyosis say that their dry skin or patches are sometimes itchy. 
  • Small, thick, or differently shaped nails. This can affect toenails and fingernails.
  • Needing more food. It takes your body a lot of energy to grow the extra skin cells that people with harlequin ichthyosis have. You might need extra food and vitamins and have trouble gaining weight.
  • Eye problems. People with harlequin ichthyosis are more likely to have different kinds of eye issues, including eye infections and twitches.

Is harlequin ichthyosis painful?

Pain management is an important part of care for people with harlequin ichthyosis. In the NICU, doctors and nurses watch babies with harlequin ichthyosis carefully for signs of pain, including crying, heart rate, and blood pressure. Babies may have pain from deep cracks in the thick plates of skin, the feeling of skin peeling off, and tight skin pulling or starting to cut off blood flow to different parts of their bodies.

Babies’ pain gets better after the thick plates of skin they’re born with fall off and the cracks heal. Your baby’s doctor will give them pain medicines such as acetaminophen (Tylenol), nonsteroidal anti-inflammatory drugs (NSAIDs, like naproxen or ibuprofen), or narcotics, depending on how much pain they are in. Sometimes, babies can look like they are in pain because of how the casing pulls their eyes and lips back, making it hard for them to move their face, and impacting their breathing. It’s important to remember that this part of how they look will go away with time and that their pain can be kept under control.

Some of the things that you do to care for a baby or child with harlequin ichthyosis may also help ease their pain. Examples include keeping a newborn in an incubator with a lot of humidity to moisten their skin, eye drops to stop their eyes from getting dry, splints to make sure their blood gets to all their limbs, fingers, and toes, and using moisturizers to soothe their skin.

Harlequin ichthyosis is caused by changes to the ABCA12 gene. This gene tells your body how to bring certain fats, called lipids, to the outer layer of your skin. In individuals with harlequin ichthyosis, a change to the gene, called a mutation, makes it work too hard. Too many lipids get sent to your skin too quickly. As they build up, the outer layer of skin becomes much thicker than usual, causing it to split up into scaly plates.

Harlequin ichthyosis is a genetic condition. To get it, the baby needs to inherit a mutated ABCA12 gene from both parents. Here’s how it happens:

Everyone has two copies of the ABCA12 gene, one from each of their parents. If only one of your copies of the gene has the mutation that causes harlequin ichthyosis, you will be a carrier. This means that you don’t have it yourself, but you can pass the gene for it on to your children. If two people who are both carriers have a child together, there is a 1 in 4 chance that their baby will have it and a 50% chance that their baby will be a carrier.

Because harlequin ichthyosis is so rare, most people don’t get tested to find out if they are carriers of the ABCA12 gene mutation. Carriers don’t have any symptoms, so they have no way of knowing. If anyone in your family has harlequin ichthyosis, or if you have had a child with it before, talk to your doctor or a genetic counselor about getting genetic testing.

Because the casing of thickened skin they’re born with gives babies with harlequin ichthyosis a very specific appearance, doctors can usually diagnose it by looking at them. If your doctor thinks that your baby has harlequin ichthyosis, they will do genetic testing to confirm it. This testing looks closely at the ABCA12 gene, which is changed (mutated) in people with harlequin ichthyosis. Genetic testing will give your doctor some information about what to expect, but it can’t predict everything.

If you have had a baby with harlequin ichthyosis before, or anyone in either parent’s family has it, you can get genetic testing to find out if you’re a carrier. If both parents are carriers, your doctor or genetic counselor can talk to you about technologies like IVF that create embryos in a doctor’s office or fertility center. They can then test the embryos to see if they have harlequin ichthyosis, and only implant the embryos that don’t.

Is there prenatal testing for harlequin ichthyosis?

Yes, now that scientists know which gene causes harlequin ichthyosis, you can get tested while you are pregnant to find out if your fetus (baby) has it. Your doctor or midwife will use a long, thin needle to take a small sample of either the placenta or the amniotic fluid that the baby floats in.

Both the placenta and the amniotic fluid have cells from the fetus in them, and your doctor can check these cells for the gene that causes harlequin ichthyosis. But if you have these samples taken for another reason, they might not check them for harlequin ichthyosis because it’s so rare. If you have had another baby with harlequin ichthyosis, or anyone in either parent’s family has it, make sure to tell your doctor so they can look specifically at this gene.

Sometimes, people find out that their baby might have harlequin ichthyosis when they get an ultrasound. This is because fetuses with harlequin ichthyosis start getting a layer of thickened skin on their bodies at about 22-24 weeks of pregnancy. The thickened skin pulls back on their eyes and lips and might make it harder for them to grow. These changes to how they look can be a clue for doctors.

Some other differences that an ultrasound can show include:

  • Extra amniotic fluid

  • Peeling skin

  • A flatter nose than other people in their family

  • A mouth that stays open

  • A larger tongue than other fetuses

  • Differently shaped ears

  • Still, clenched hands or feet if the tight, thickened skin makes it harder for them to move

  • Being smaller than expected for their age

  • Extra pieces of skin floating in the amniotic fluid (called snowflake sign)

3D ultrasound can make these differences easier to see. These changes are seen in the second or third trimester.

If your doctor or midwife sees changes on an ultrasound that might be related to harlequin ichthyosis, they will send you to get genetic testing for the fetus.

Care for both premature babies and babies with harlequin ichthyosis has gotten much better over the years. Harlequin ichthyosis is life-threatening, and in the past, most babies who had it only lived a few days. Thanks to a new kind of medicine called retinoid therapy, as many as 80%-90% of newborns with harlequin ichthyosis survive. Worldwide, a little over half of all babies with harlequin ichthyosis live; this is because retinoid therapy and intensive care aren’t available everywhere.

The first few weeks are the most dangerous for such babies and they need to be in a NICU. The NICU’s round-the-clock care will help manage any of your baby's health challenges, which can include:

  • Premature birth
  • Low temperature, or problems keeping their body at the right temperature
  • Dehydration
  • High levels of salt (sodium) in their blood
  • Problems breathing, they might need a breathing tube
  • Infections in their skin, eyes, lungs, and other places
  • Risk of eye damage if their eyelids can’t close
  • Trouble nursing or taking a bottle because the thick skin pulls their lips and mouth back and makes it hard for them to suck. This can lead to them not getting enough food.
  • Risk of hearing problems

Over the first few weeks, the thick layer of scaly outer skin that babies are born with falls off. It gets replaced with new, softer skin. Survival rates go up after this happens.

People who are born with harlequin ichthyosis will have it for their whole lives, and they will need to carefully manage this chronic health condition. But more and more people with harlequin ichthyosis are living to be adults, and some of them have kids of their own.

Treatment for harlequin ichthyosis focuses on managing the symptoms, keeping the skin as protected as possible, and preventing infection. It will not make harlequin ichthyosis go away, but it can help people who have it live longer and be more comfortable.

Treatment in the NICU

Babies born with harlequin ichthyosis need special care in the NICU. For them, the most dangerous time is the first few weeks of life, before the thick casing they’re born with falls off.

In the NICU, doctors and nurses will watch your baby constantly and give them round-the-clock care. Your baby might also get support from physical and occupational therapists, skin doctors (dermatologists), nutritionists, or other professionals. Here are some of the things they might do to help your baby:

  • Retinoid therapy. Your baby will probably get a kind of medicine called retinoids, either as a syrup they swallow or as a cream that goes on their skin. Retinoids help the casing fall off and the skin underneath repair itself, and they have made it possible for many babies to survive. They do have side effects, though, so your baby will be watched closely, and they will stop giving them retinoids as soon as they can. Your baby’s doctor will tell you about the risks and what they will do to keep your baby safe. 
  • Skin care. Nurses will put special creams on your baby to moisturize the cracks and help create a “wall” between the baby’s body and the outside world. This also helps seal in moisture so your baby doesn’t lose water. NICU staff will check for skin infections, which are common in babies with harlequin ichthyosis. They might put antibiotic ointment on the cracks in your baby’s skin.
  • Baths. Your baby will get special baths at least once a day, to help soften the thick plates of skin in the casing. NICU staff might put medication to prevent infection in the bath.
  • Moist environment. The baby’s incubator or crib will be kept very humid to make up for water that might leak out of the cracks in their skin. This also helps keep the skin as comfortable and moisturized as possible. 
  • Warmth. Babies with harlequin ichthyosis have trouble keeping their bodies at the right temperature because heat leaves through the cracks in their skin. NICU staff will watch your baby’s temperature and make sure they are warm enough.
  • Help breathing. The casing of tight skin around the baby’s belly and chest might make it hard for them to breathe. As most babies with harlequin ichthyosis are born too early (premature), their lungs might not be all the way developed yet. Your baby might need oxygen or a breathing tube.
  • Help eating. Many babies with harlequin ichthyosis have trouble feeding because the casing pulls their lips back tightly and makes it hard to move their mouth. If they can’t nurse or take a bottle, their doctor might put a small tube into their stomach. They will be fed through this tube until the skin around their mouth and lips heals and they can suckle on their own.
  • Water and nutrition. Making extra skin cells takes a lot of energy, and babies with harlequin ichthyosis need extra food and vitamins. NICU staff will make sure your baby gets all the nutrition and vitamins they need. They’ll check your baby’s weight and full diapers, and they might do blood tests. This helps them check for dehydration.
  • Looking out for infection. If your baby shows any signs of an infection, they might get antibiotics or other medicines. 
  • Checking arms, legs, fingers and toes. The casing can cut off blood flow to these body parts, or cause them to be curled up tight in odd positions. It can also make it hard for the baby to move. For this reason, NICU staff will keep a close eye on your baby’s arms, legs, fingers, and toes. They might need special splints or physical or occupational therapy to keep their blood flowing well and help them move better. Sometimes, doctors will do a small surgery to free up their arms, legs, fingers, or toes. 
  • Eye care. Your baby will get eye drops to keep their eyes from drying out. If they develop eye infections or other problems, they will get antibiotics. 
  • Pain control. NICU staff will watch your baby closely for signs of pain, and come up with a pain management plan to keep them comfortable. Your baby might get acetaminophen (Tylenol), nonsteroidal anti-inflammatory drugs (NSAIDS, like ibuprofen or naproxen), or narcotics. 
  • Emotional support and education. Having a baby in the NICU is often hard on families, and you might get visits from social workers or other professionals who look out for your family’s well-being. Nurses and other professionals will also help you learn more about what to expect and how to care for your baby with harlequin ichthyosis. They can help you bond with your baby and get ready for the future. They recommend touching your baby as much as possible. They may be able to tell you about other families who have children with harlequin ichthyosis.

Home management after the NICU

Even after the casing they’re born with falls off, people with harlequin ichthyosis will have thick, dry skin that needs extra care. They might also have other symptoms and challenges. After they go home from the NICU, treatment focuses on keeping their skin as moisturized as possible and managing symptoms. It includes:

  • Baths. Bathing frequently helps keep your skin soft and loosens the thick plates that develop. In addition to soaking in the bath, you can use a loofah or sponge to gently remove plates and dry skin. Some people add disinfectants to their baths to prevent infection.
  • Skin care. Putting moisturizer or petroleum jelly all over your body several times a day helps stop your skin from getting too dry. It also creates a wall between your body and the world, preventing cracks. Many people have to experiment with different products to find the ones that work best for them. Finding a skin doctor, called a dermatologist, who knows how to take care of people with harlequin ichthyosis is important. Your dermatologist can recommend skin care products and help you manage the condition.
  • Watching out for infections. People with harlequin ichthyosis are more likely to get infections. Keeping the skin moist and removing patches will help prevent cracks that can let germs in and cause infections. See a doctor right away if you see any symptoms of infection.
  • Joints and moving. Some doctors think that people with harlequin arthritis are more likely to get arthritis. Dry, tightened skin on your joints or the soles of your feet can make walking harder. You might also have trouble with fine motor skills such as picking things up or writing. Your doctor might send you to a joint specialist (rheumatologist), dermatologist, physical therapist, or occupational therapist to get help with this. You may need splints, wheelchairs, or other equipment.
  • Prevent overheating. Thickened skin can get in the way of being able to sweat, which makes people with harlequin ichthyosis more likely to overheat. Stay in the shade when it’s hot out, and wear sunscreen and clothes that protect you from the sun. Drink plenty of water and watch out for dehydration. Many people with harlequin ichthyosis are also sensitive to the cold. You might need extra warm layers and more moisturizer in cold weather.
  • Ear care. Extra skin can build up inside the ears and impact hearing. People with harlequin ichthyosis should see an ear, nose, and throat doctor and get regular hearing tests.
  • Eye care. Many people have ongoing eye problems related to how their eyelids were pulled tight and held open by the casing when they were born. See an eye doctor regularly and get screened for problems with your vision. If your eyes are dry, it can help to use eye drops or ointment.
  • Extra nutrition. People with harlequin ichthyosis need extra food and vitamins because their bodies use so much energy making extra skin cells. Your doctor or nutritionist can help you make sure you get enough food and nutrients to prevent problems.
  • Emotional and social support. People with harlequin ichthyosis have a unique appearance. Other people might be curious, uncomfortable, or even mean. Some people with harlequin ichthyosis might experience bullying. Being straightforward and letting people know that you/your child has a chronic health condition may help them understand. As much as possible, try to build self-confidence and social support. It might help to connect with a support group for people with ichthyosis and their families, other people with the condition, or a mental health professional.

Harlequin ichthyosis is a very rare and serious genetic condition that causes you to grow too much skin. Babies with this condition need round-the-clock care in a NICU. Thanks to new medicines and better NICU care, more babies with harlequin ichthyosis survive the first few weeks after they are born, which is the most dangerous time. With careful attention to taking care of their skin and managing other symptoms, people with harlequin ichthyosis can live a long time and have a good quality of life.

  • What is the life expectancy of people with harlequin ichthyosis?

    In the past, most babies with harlequin ichthyosis died a few days after they were born. Now, doctors have gotten better at caring for them, and many more babies survive. A new kind of medicine, called retinoid therapy, helps babies with this condition live through the first few weeks, until they shed the casing of thick skin they’re born with. Once the casing sheds, they are more likely to survive.

    Since retinoid therapy started being used on babies with harlequin ichthyosis in the early 2000s, more and more babies have lived. But not enough time has gone by since then to figure out the average lifespan for newborns with harlequin ichthyosis who survive the first few weeks. In 2011, scientists looked at 45 people who were born with harlequin ichthyosis. Their ages ranged from 10 months to 25 years old. It’s possible that many of them are still alive.

    Some doctors think that people with harlequin ichthyosis who live past the first few weeks can have the same lifespan as anyone else.

  • Who is the oldest survivor of harlequin ichthyosis?

    Most often, scientists have focused on studying newborns with this condition. They know less about older children and adults. We do not have any formal ways of tracking older people with harlequin ichthyosis, so it's hard to know who the oldest person with it is.

    Nusrit Shaheen, a children’s sports coach who lives in England, was born in 1984. She is thought to be the oldest person with harlequin ichthyosis in the United Kingdom. Mui Thomas is a rugby referee and yoga teacher in Hong Kong, and she is in her early 30s.

    In 2023, doctors in China wrote about two siblings who were 57 and 59 years old; they both had harlequin ichthyosis. There might be other people who choose to stay private.

  • Can harlequin ichthyosis be cured?

    There is no cure for harlequin ichthyosis. People who are born with it will have it their whole lives. But it can be managed, like other chronic diseases and conditions. Treatment for it is about taking care of symptoms and helping people be more comfortable.

  • Why do babies with harlequin ichthyosis have red eyes?

    When they are born, babies with harlequin ichthyosis are covered in a tight layer of thickened, plate-like skin. The tight covering pulls back their eyelids all the way so that you see the red inner lining. This gives their eyes a red look. As they shed the covering, their eyelids won’t be pulled back anymore, and they will be able to close their eyes. Their eyes won’t look as red when you are able to see their skin-colored outer eyelids.

Print
View privacy policy, copyright and trust info
View privacy policy, copyright and trust info