Introduction
Harlequin ichthyosis is a serious genetic condition that mainly impacts the skin. Upon birth, infants affected with this disorder display sheets of thick skin that exhibit cracking and separation. These substantial plates can exert force on facial features, distorting them, and also may hinder respiration and feeding in newborns. Harlequin ichthyosis arises due to genetic mutations in the ABCA12 gene, and its inheritance follows an autosomal recessive pattern. Symptoms usually start appearing as soon after birth. Symptoms can vary among different diseases, occurring within distinct age ranges. Some diseases exhibit symptoms within a specific age range, while others may manifest at multiple points in a person’s life. In certain cases, symptoms can emerge at any age. Determining the onset of symptoms is crucial for healthcare professionals in accurately diagnosing medical conditions.
What Are the Features of Harlequin Ichthyosis?
Harlequin ichthyosis refers to a group of genetic disorders and is a type of ichthyosis that is characterized by scaly, dry, thickened, and cracked skin. The following are the features of Harlequin ichthyosis:
1. Thick Plate-Like Scallions: Newborns affected by Harlequin ichthyosis exhibit dense, plate-like scales encircling the whole body. These scales have the potential to fissure and fracture, resulting in painful and infection-prone deep crevices.
2. Distorted Facial Features: This condition can result in the distortion of facial features due to skin tightness. Ears and eyelids may protrude, while the lips might be drawn tight, making it difficult for the mouth to open.
3. Restricted Movement: Pronounced skin thickening and constriction can pose challenges to the movement of the eyes, mouth, limbs, and other body parts, thereby making movement difficult.
4. Eye and Ear Abnormalities: Harlequin ichthyosis affects the ears and eyes. Ectropion is an eye condition that can turn the eyelids outward, resulting in dryness and exposure of the eyes. Also, the ears may exhibit deformities attributed to the thickened skin.
5. Increased Risk of Infection: The skin, with its cracks and fissures, becomes susceptible to bacterial and fungal infections. Babies affected by Harlequin ichthyosis often necessitate careful skin care to avert infections.
6. Respiratory Difficulties: There can be breathing challenges in infants due to increased skin thickness near the chest area. In severe instances, this can result in respiratory distress, necessitating the need for immediate medical intervention.
What Is the Genetic Basis of Harlequin Ichthyosis?
Harlequin ichthyosis follows an autosomal recessive inheritance pattern, often pointing to consanguinity among parents as a cause. Individuals with the condition have a homozygous presentation of a nonsense mutation in the ABCA12 gene, which stands for adenosine triphosphate-binding cassette transporter, subfamily A, member 12. This genetic alteration located on chromosome 2q33-q35 leads to the premature cessation of protein translation.
The ABCA12 gene has a critical function in conveying lipids to diverse cells throughout the body, and these lipids are essential for the normal development of the epidermis. Regrettably, close to 50 percent of infants born with this condition do not survive, primarily due to a variety of complications such as severe dehydration, respiratory failure, sepsis, hypoglycemia, hypothermia, and renal failure.
How Is Harlequin Ichthyosis Diagnosed?
Timely perinatal diagnosis holds significant importance. It involves examining amniotic fluid cells and conducting ultrasounds, with a particular focus on the fetal mouth, typically around the 17th week of pregnancy. These methods have demonstrated their effectiveness in providing conclusive results. Furthermore, obtaining a comprehensive family history, information about previous pregnancies, including any consanguinity between parents, and whether other children have had any inherited dermatological conditions is crucial.
In the postnatal period, diagnosis typically involves a skin biopsy, which is expected to reveal structural abnormalities in lamellar granules and epidermal keratin expression. In many cases, the overall appearance of the fetus at birth can also be indicative enough to make a diagnosis.
How Is Harlequin Ichthyosis Managed?
Given the complexity of complications and associated comorbidities, a multidisciplinary approach is essential. Initial management involves placing the infant in a humidified incubator to mitigate transcutaneous water loss, along with physiotherapy, providing analgesia to alleviate pain from deep fissures, maintaining stringent infection control measures, and ensuring adequate nutrition. A comprehensive case series involving 45 individuals has suggested the use of oral retinoids, with a preference for Acitretin. Acitretin operates by facilitating the shedding of hyperkeratotic encasement, triggering a phenotypic switch that aids in enhancing survival.
Opting for Acitretin is substantiated by its advantageous side effect profile and a comparatively shorter half-life. During the first month of life, when deep fissures are still healing, the risk of sepsis remains a significant concern and regrettably stands as the primary cause of mortality in these patients. Surprisingly, there is a lack of supporting data for antibiotic therapy in these cases.
What Is the Prognosis of Harlequin Ichthyosis?
Harlequin ichthyosis is linked to significant morbidity and mortality, particularly in the early stages of life, with approximately 50 percent of affected infants facing these challenges. This high risk is primarily due to the potential for sepsis and respiratory failure, which accounts for about 75 percent of the cases. However, for those who survive this critical period, it is possible to have a normal life expectancy. Nonetheless, they may encounter substantial skin-related issues, including persistent ectropion, developmental and motor milestones that are delayed, and difficulties in social interactions. Current medical treatments have led to substantial improvements in both the quality and expectancy of life for individuals with Harlequin ichthyosis. Nevertheless, the disease’s severity can still impact life expectancy. Ongoing research is evaluating the prognosis of the disease with these contemporary treatments to gain a better understanding of the long-term outcomes.
Conclusion
Harlequin ichthyosis is an uncommon genetic skin disorder. Parents at risk should be strongly recommended for prenatal diagnosis, genetic counseling, and genetic screening. The primary approach to management remains supportive therapy. Unfortunately, the prognosis for neonates with this condition is not very promising. For those who survive the critical newborn period, the condition tends to become less severe. However, developmental delays, including both motor and social skills, persist. Fortunately, these children typically catch up to their peers in terms of mental development. It is worth noting in the past, babies affected by this condition rarely survived beyond a few days. Thanks to medical advancements, there is now a greater chance for infants with Harlequin ichthyosis to lead longer lives.
