What are the other Names for this Condition? (Also known as/Synonyms)

• Harlequin Baby Syndrome
• Ichthyosis Congenita, Harlequin Fetus type
• Ichthyosis Fetalis

What is Harlequin Ichthyosis? (Definition/Background Information)

• Harlequin ichthyosis is a very uncommon congenital disorder of skin characterized by dry scaly skin that form plates on the body resembling fish scales. It is a serious medical disorder causing breathing and eating difficulties 
• Harlequin Ichthyosis can also result in dehydration, body temperature issues, infections, including sepsis, and even preterm birth. It is a genetic condition that is inherited in an autosomal recessive manner
• Presently, there is no cure for Harlequin Ichthyosis; symptomatic treatment and supportive care is normally provided that includes topical agents, oral retinoids, and antibiotic therapy. Children who are able to survive the first few years generally see an improvement in their condition, although the quality of life may be severely affected

Who gets Harlequin Ichthyosis? (Age and Sex Distribution)

• Harlequin Ichthyosis is an extremely rare congenital disorder. An incidence rate of 1 in 300,000 births is noted
• The presentation of symptoms are seen following the birth of the child
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Harlequin Ichthyosis? (Predisposing Factors)

• A positive family history may be an important risk factor, since Harlequin Ichthyosis is an inherited condition
• Currently, no other risk factors have been clearly identified for this skin condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Harlequin Ichthyosis? (Etiology)

Harlequin Ichthyosis is an autosomal recessive disorder that is caused by mutations in the ABCA12 gene.

• The ABCA12 gene encodes for the ABCA12 protein that is critical for skin cell development and transport of lipids to the epidermal layers of skin
• When there is a disruption in the process, the normal development of the outermost skin layers is affected leading to the formation of thick scaly skin and consequent issues

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Harlequin Ichthyosis?

The signs and symptoms of Harlequin Ichthyosis may include:

• Thickened skin covering the entire body at birth; the skin form like plates that crack and split
• Large diamond or rectangle-shaped skin plates separated by deep cracks
• The shape of the eyelids, nose, mouth, and ears may be abnormal due to skin distortion
• Limited movement of the arms and legs (joint mobility)
• Breathing difficulties due to restricted chest movement
• Recurrent respiratory infections
• Feeding problems
• Hearing impairment
• Congenital ichthyosiform erythroderma
• Severe dehydration from loss of body fluids
• Cataract 
• Heat and cold intolerances

How is Harlequin Ichthyosis Diagnosed?

The diagnosis of Harlequin Ichthyosis may involve the following tests and exams:

• Physical examination of the individual and medical history evaluation
• Assessment of the presenting signs and symptoms
• Dermoscopy: Dermoscopy is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Skin biopsy, if necessary: A skin biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis
• Prenatal testing including abdominal ultrasound scans, amniocentesis, or chorionic villus sampling
• Molecular genetic testing to check for or confirm specific causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Harlequin Ichthyosis?

The complications of Harlequin Ichthyosis may include:

• Severe emotional distress for the parents and caregivers of the child
• Malignant hyperthermia 
• Respiratory insufficiency 
• Self-injurious behavior 
• Premature birth
• Entire skin of the body can be severely affected
• Severe eating, swallowing, and breathing difficulties in children
• Increased risk for severe infections
• Malnourishment
• Decreased quality of life
• Sudden cardiac death

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Harlequin Ichthyosis Treated?

There is no cure for Harlequin Ichthyosis since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops. This may include:

• Moisturizing creams and petrolatum
• Antibiotics
• Oral or intravenous etretinate or retinoids
• Use of humidified incubator
• Nutritional support through feeding tubes
• The child is usually placed in a neonatal intensive care unit for treatment and support
• Surgical debridement of necrotic skin tissues

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

How can Harlequin Ichthyosis be Prevented?

Currently, Harlequin Ichthyosis may not be preventable since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Harlequin Ichthyosis? (Outcomes/Resolutions)

• The prognosis of Harlequin Ichthyosis is primarily dependent upon the severity of the signs and symptoms and associated complications. In many cases, the prognosis is poor
• However, if children are able to cope with appropriate intensive therapy during the first few years of life, then an improvement is noted in the condition and the skin generally heals to result in a severe (but more manageable) ichthyosiform erythroderma

Additional and Relevant Useful Information for Harlequin Ichthyosis:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/healthy-living/skin-disorders/