Disease Overview
Disease name: Harlequin ichthyosis, which is also known by other terms like ichthyosis fetalis and harlequin baby syndrome.
Affected Populations
This genetic condition is reported to affect approximately 1 in 300,000 live births worldwide. In the United States, the frequency is closer to 1 in 500,000, translating to about seven instances each year. Data from the National Organization for Rare Disorders indicates that the condition impacts both males and females equally, without favoring any specific racial or ethnic group.
Causes
Harlequin ichthyosis arises from various mutations in the ABCA12 gene. This gene holds instructions for proteins responsible for transporting molecules through cell membranes. These proteins are crucial for moving fats and enzymes in the skin’s outer layer, known as the epidermis.
Most individuals with this condition possess a genetic mutation that leads to the production of ABCA12 proteins that are either too short or entirely absent, which severely hampers their ability to transport fats. In certain situations, individuals may not produce the protein at all, leading to the more severe manifestations of the disease.
It’s suggested that this condition follows an autosomal recessive inheritance pattern, meaning that a child must inherit two copies of the faulty gene—one from each parent—to develop the disorder. Those carrying just one mutated gene don’t exhibit symptoms but can be carriers. If there’s a family history of the condition, genetic counseling might be advisable to determine carrier status.
Symptoms
The effective transportation of fat molecules in the epidermis is vital for skin hydration and development, both in-utero and post-birth. When ABCA12 proteins are either too short or absent, newborns may present with thick, plate-like scales of skin that cause a tight stretch. This tightness can lead to skin cracking and fissures.
This tension can also cause the eyelids and lips to turn inside out and may restrict chest movement, making it challenging for the baby to breathe and eat. Reduced hair and nail growth are also frequent complaints.
Often, babies with harlequin ichthyosis are born prematurely, displaying additional signs like a flat nose, hearing abnormalities, ears fused to the head, swollen extremities, and limited joint mobility.
The compromised skin barrier leaves infants susceptible to dehydration and makes temperature regulation and infection fighting particularly difficult. For those who survive the early days, the “armor-like” plates may eventually shed, leaving behind skin that is red, dry, and scaled.
While many infants with harlequin ichthyosis do not survive the newborn phase, some can live into later infancy, childhood, or even early adulthood with intensive medical support. A study examining 45 cases found that around 55% of patients made it through the newborn period, with survivors ranging from 10 months to 25 years old. Common causes of death shortly after birth include respiratory failure and sepsis.
Treatments
Currently, there is no cure for harlequin ichthyosis; treatment focuses on symptom management.
According to the Cleveland Clinic, affected infants are typically admitted to the neonatal intensive care unit (NICU) right after birth. In the NICU, they might be placed in humidified incubators for temperature regulation and skin hydration. Frequent baths can help soften and detach the skin plaques, while exfoliation techniques may be employed to remove scales. Moisturizers and skin barrier products are beneficial in managing dryness and rigidity, and pain relievers can assist with the infants’ comfort.
In severe situations, retinoids might be prescribed, which are usually administered orally. These medications help to diminish the thick scales, potentially improving other experienced symptoms; however, they’re reserved for severe cases due to potential toxic side effects from prolonged use.
Antibiotics may be necessary to prevent or treat skin infections, and regular lubrication for the eyes is important, as affected infants often can’t close their eyelids properly.
Once they leave the NICU, children with harlequin ichthyosis need continuous skin care and regular medical attention to manage any emerging symptoms. This typically involves a wide-ranging team of medical professionals, including ophthalmologists, plastic surgeons, nutritionists, and physical and occupational therapists.
