What Is Harlequin Ichthyosis?

Harlequin ichthyosis is a rare genetic disorder that affects the skin. It causes thick plates of skin with deep cracks between the plates. Harlequin ichthyosis affects fewer than 200,000 people in the United States.

In the past, infants born with harlequin ichthyosis did not survive the newborn period, but treatment options have improved. Now with neonatal intensive care unit (NICU) care, it is possible to live into childhood or adulthood.

This article provides an overview of harlequin ichthyosis, including the symptoms, causes, and treatment options.

Types of Ichthyosis

Ichthyosis is a group of skin disorders that cause dry, scaly patches of skin. Harlequin ichthyosis is the most severe type. These conditions are genetic and caused by autosomal recessive mutations. 

Symptoms of ichthyosis can range from mild to severe. Harlequin ichthyosis leads to several serious complications, including water loss, dehydration, the inability to regulate temperature, and infections.

There are more than 20 types of ichthyosis, including:

• Ichthyosis vulgaris is the most common type that causes mildly dry, flaky skin.
• Epidermolytic ichthyosis is present at birth and causes blisters all over the body.
• Lamellar ichthyosis occurs at birth and causes a tight, clear covering over the body called a collodion membrane. 
  

Harlequin Ichthyosis Symptoms

Infants with harlequin ichthyosis are often born prematurely with hard, thick skin plates separated by deep cracks known as fissures. It affects the shape of the facial features because these thick skin plates pull on the eyelids, nose, and mouth. It also restricts an infant’s mobility. 

Other symptoms of harlequin ichthyosis include:

• Red, scaly skin 
• Depressed nasal bridge (the nose appears flattened to the face)
• Eyelids turned out
• Ears fused to the skin
• Hearing changes
• Frequent respiratory infections 
• Outward turned lips
• Feeding difficulties 

Less common symptoms may include:

• Cataracts
• Shortness of breath
• Self-injurious behavior (deliberately hurting your body)
• Sudden cardiac failure 

After the newborn period, the thick skin plates shed, and the skin develops scales and redness.

Causes

Harlequin ichthyosis is a genetic disorder caused by a variant or mutation in the ABCA12 gene. This gene gives the body instructions for making a protein for developing skin cells. It plays a vital role in transporting fats and enzymes in the epidermis (the outermost layer of skin).

Harlequin ichthyosis is inherited as an autosomal recessive pattern, which means a child with this condition inherits two mutated cells, one copy from each parent. Carriers with one mutated gene do not have signs or symptoms of the disease.

When both parents are carriers of harlequin ichthyosis, the risk of having a child with the condition is 25%. The risk of having a child carrier is 50%, and the risk of having a child with two healthy copies of the ABCA12 gene is 25%.

Diagnosis

Most infants with harlequin ichthyosis are diagnosed at birth based on their appearance. 

This condition may be detected with prenatal testing based on fetal DNA. It is sometimes detectable on ultrasound in the second or third trimester.

Treatment

Harlequin ichthyosis requires immediate treatment at birth. Infants are taken directly to the NICU when they are born. The goal of treatment is to reduce the risk of infection by keeping the skin moisturized to prevent cracking and fissuring.

Infants with harlequin ichthyosis require medical care from pediatricians, geneticists, dermatologists, ophthalmologists, and neonatologists. After the newborn period, the thick skin plates will eventually split and peel off. Once this occurs, the skin will be red, dry, and covered in large skin scales.

Treatment for harlequin ichthyosis includes:

• NICU care: Infants require one-on-one nursing care for their first several weeks.
• Rehydration: Dehydration is a serious concern when the skin barrier is interrupted.
• Prevention of infection: The first few weeks of treatment include antibiotics and careful skin care to help reduce infection risk.  
• Temperature control: After birth, infants are placed in a high-humidity environment in a heated incubator.
• Nutritional support: Infants with harlequin ichthyosis have increased nutritional needs.

Skin care is also a vital part of harlequin ichthyosis treatment, including: 

• Skin-softening agents: Oral Soriatane (acitretin) may accelerate skin shedding. 
• Gentle exfoliation: Removes the thick scales of skin.
• Skin barrier repair: Products that contain ceramides or cholesterol can help repair the skin.
• Gentle moisturizers: Products with petroleum or lanolin can add moisture to the skin.
• Mild keratolytic: Products with alpha-hydroxy acids or urea can help to remove the skin scales.
• Eye care: If an infant’s eyes are pulled open, their corneas must be lubricated and protected.

Prognosis 

The prognosis for infants with harlequin ichthyosis depends on the severity of the disease and how quickly it is treated. In the past, the prognosis was poor, and infants did not survive beyond the newborn period. 

To improve an infant’s prognosis, they need to be in the NICU as soon as they are born. This is the area of the hospital where the healthcare providers have the most expertise and tools to care for a critically ill child. With NICU care and effective treatment, infants with harlequin ichthyosis can live into their teens and adulthood with this disorder. 

Coping 

Harlequin ichthyosis is a severe genetic disorder that significantly impacts an infant’s life and the lives of their loved ones. Parents and caregivers need resources and tools to care for a seriously ill child. 

Many organizations offer support groups and other resources for parents of children with harlequin ichthyosis, for example, the Foundation for Ichthyosis and Related Skin Types and Ichthyosis Support Group.

Summary

Harlequin ichthyosis is a rare, severe genetic disorder that affects the skin. Infants born with this condition have thick plates of dry skin separated by deep cracks. They are at risk of several complications, including dehydration and infection.

The goal of harlequin ichthyosis treatment is to prevent infection. Upon birth, infants are transferred to the NICU for critical care, skin care, temperature control, nutritional support, and antibiotics. 

A Word From Verywell 

Harlequin ichthyosis is a serious disorder that significantly impacts an infant and their family. Learning that your child has a rare genetic disorder is a life-changing experience. Seeking support and resources for your family will be important for your journey. Talk with your child’s healthcare team about support groups, financial resources, and any other questions you have.