Introduction
Harlequin fetus (Harlequin ichthyosis) is a rare, severe genetic disorder that mainly affects the skin of a newborn. It is an autosomal recessive disease that affects one in five lakh live births. The newborn infant's skin is covered with diamond-shaped plates like fish scales. It affects the shape of the nose, eyelids, ears, and mouth, interfering with the movement of arms and legs. In addition, thick, hard skin plates on the face and chest cause breathing difficulties. Thus, newborns with Harlequin ichthyosis need immediate neonatal care unit management. Even though the Harlequin fetus is a severe medical condition, recent advances in the field of modern medicine have made an improved response to treatment and life expectancy.
What Is a Harlequin Fetus?
Harlequin fetus is a severe form of ichthyosis with extreme skin dryness and scaling all over the body. In this condition, newborn infants are born prematurely with hard trapezoid or diamond-shaped heavy skin plates separated by deep cracks. These skin abnormalities disrupt the shape of the nose, eyelids, ears, and mouth, resulting in abnormal facial features. Thickened skin over the nose and chest interferes with normal respiration and causes breathing difficulties and feeding problems.
Abnormally hard skin plates in the entire body disrupt normal protective functions of the skin and result in recurrent infections, water loss, and altered body temperature. After the newborn period, the skin plates usually shed, leaving widespread redness and scales. Improved medical care and support are needed for the infants to survive the initial days and improve overall health.
What Are the Causes of a Harlequin Fetus?
Harlequin fetus (Harlequin ichthyosis) occurs due to variations (mutation) in the function of the ABCA12 gene. This gene plays a vital role in regulating protein synthesis and skin development. The ABCA12 gene instructs the production of ABCA12 proteins that promote the transport of lipids and enzymes in the outermost skin layers, essential for developing normal skin cells. Any alterations in the response of the ABCA12 gene lead to abnormality in the protein and disrupted lipid transport in the skin. Altered ABCA12 protein causes abnormal development and functions of the epidermis (outer skin layer), resulting in skin abnormalities of the Harlequin fetus.
What Are the Symptoms of a Harlequin Fetus?
In the Harlequin fetus, newborns present with hard, fissured skin with hyperkeratosis. Other than skin disorders, these infants may have poor mental and physical development. Children born with Harlequin ichthyosis usually present with severe facial and cranial deformities.
Clinical symptoms present in the Harlequin fetus are the following:.
- Red, scaly skin.
- Poorly developed ears.
- Everted eyelids (ectropion).
- Flat nose.
- Frequent respiratory infections.
- Swollen hands and feet.
- Inability to close eyelids.
- Low body temperature.
- Severe dry skin.
- Recurrent eye infections.
- Deformed lips.
- High sodium content in the blood.
- Nursing difficulties.
- Small hands and feet.
- Fused ears.
- Open mouth.
- Dry mouth.
- Underdeveloped fingers.
- Lack of regular muscle movements.
- Thin or sparse hairs.
- Thick fingernails.
- Abnormal facial features.
- Reduced finger movements.
- Hearing problems.
- Skin infections.
- Cracked skin.
- Temperature sensitivity.
- Dehydration.
- Difficulty in breathing.
- Respiratory failure.
How Can We Diagnose a Harlequin Fetus?
A harlequin fetus is diagnosed based on their physical appearance during birth. Physical examination of the characteristic features of Harlequin ichthyosis (hard deep diamond skin plates) is helpful for an initial diagnosis. Some laboratory tests can also be done with a physical examination to confirm the Harlequin fetus. Genetic testing accounts for the most specific test and reveals mutation and loss of function of the ABCA12 gene. In addition, histological changes associated with skin can be identified using skin biopsy. Prenatal testing for Harlequin ichthyosis can be done by testing mutations in the ABCA12 gene in the fetal DNA (deoxyribonucleic acid). Some features associated with Harlequin ichthyosis can be seen on ultrasound radiographs during pregnancy (second trimester).
What Are the Treatment Options for Harlequin Fetus?
A multidisciplinary medical team manages the Harlequin fetus. After birth, the baby receives immediate neonatal intensive care unit (NICU) facilities. After early intensive treatment, lifelong care is needed to improve the baby's overall condition.
The steps involved in the treatment of the Harlequin fetus are as follows:
- Initial Emergency Management - As soon as the baby is born with Harlequin ichthyosis, intensive care is provided to reduce complications and improve outcomes. Specific management is also needed for respiratory distress, feeding difficulties, dehydration, electrolyte imbalance, infections, and thermoregulation.
- Initial Treatment - Once the baby is shifted from the neonatal intensive care unit (NICU), long-term care is needed to manage their overall health. The thick skin plates will gradually peel off, exposing the inner skin layers. Therefore, extensive daily care must be done to prevent skin cracks and infections. Oral retinoids can be used in severe cases to improve outcomes. Antibiotics can also be given to avoid skin infections and further complications. Lubricating eye drops can be used to reduce dryness and irritations. Most infants born with Harlequin ichthyosis need proper medical care for several weeks of life.
- Supportive Treatment - There is no specific treatment option for the Harlequin fetus (Harlequin ichthyosis). Long-term management includes supportive care, including skin dryness reduction and infection prevention. Continuous peeling off thick plates of the skin results in dry, reddened areas, exposing the inner skin layers. Skin irritations and dryness can be reduced by applying moisturizers. It can be done after bathing while the skin is moist. Moisturizers containing ceramides, lanolin, petrolatum, cholesterol, and alpha hydroxy acids (AHAs) can prevent skin fissures and cracks. Removal of the damaged skin plates can be done in certain areas, like fingers, to improve blood circulation.
What Are the Complications of the Harlequin Fetus?
The complications of harlequin ichthyosis, which vary in severity, range from poor hair growth and nail deformities to chronic pruritus, intolerance to temperature extremes, recurrent skin infections, and electrolyte abnormalities. It also hardens and tightens muscles, tendons, skin, and other tissues, which could further limit movement. In extreme cases, it can lead to respiratory failure or abrupt, life-threatening sepsis.
Is It Possible for Babies to Survive With Harlequin Ichthyosis?
Over the years, not only has the care of premature babies improved, but so has that of babies with harlequin ichthyosis. Harlequin ichthyosis is a life-threatening condition. In older days, most of the infants affected with this disorder survived only for a few days. However, by introducing retinoid therapy, the survival rate in newborns has reached 80 percent to 90 percent. Despite this, it is still the case that, due to limited access to retinoid therapy and intensive care in some parts of the world, little more than half of all babies born with harlequin ichthyosis worldwide survive.
Conclusion
Harlequin fetus (Harlequin ichthyosis) is a rare skin disorder characterized by severe dryness and thick skin plates all over the body. It occurs due to a genetic mutation of the ABCA12 gene, which codes for skin proteins. Infants born with Harlequin ichthyosis may develop difficulty breathing and feeding due to hard skin plates over the nose, mouth, and chest. Even though it presents severe difficulties and symptoms, babies born with Harlequin ichthyosis can live up to early adulthood with intensive medical support and advanced treatment options.
