Harlequin Ichthyosis · What Is It, Causes, Signs, Symptoms, and More

Published: Oct 17, 2025

Author: Lily Guo, MD•

Editor: Alyssa Haag, MD•

Editor: Ian Mannarino, MD, MBA•

Editor: Kelsey LaFayette, DNP, ARNP, FNP-C

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What is harlequin ichthyosis?

Harlequin ichthyosis, also known as a harlequin fetus, ichthyosis fetalis, or harlequin baby syndrome, refers to a condition where infants are born with thick, hyperkeratotic scales covering their entire body. The thick layer of skin can crack and split leaving large plates of skin with fissures. Other characteristics of harlequin ichthyosis include ectropion (i.e., outward turned eyelids), disfigurement of digits on the hands and feet, and absent eyebrows and eyelashes.

Ichthyosis is a general term for a family of rare, genetic skin diseases characterized by dry, scaling, and thick skin. Harlequin ichthyosis is the most serious, potentially life-threatening form of congenital ichthyosis and is inherited in an autosomal recessive pattern. A newborn with harlequin ichthyosis may have trouble breathing and eating due to thickening of the skin on the face and have temperature dysregulation and metabolic abnormalities requiring care and treatment in a neonatal intensive care unit by a multidisciplinary team often consisting of a dermatologist, pediatrician, geneticist, and other healthcare professionals.

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What causes harlequin ichthyosis?

Harlequin ichthyosis is a genetic disorder caused by mutations in the ABCA12 gene, which encodes an adenosine triphosphate-binding cassette (ABC) transporter. Lack of this protein transporter leads to defects in lipid transport to the epidermis and atypical skin barrier formation, thereby causing characteristically thickened skin.

What are the signs and symptoms of harlequin ichthyosis?

Harlequin ichthyosis commonly occurs in newborns and results in plate-like scales covering the entire body. The plates can appear transparent, shiny, and taut. Eventually, they may dry out to form diamond-shaped plaques separated by deep red fissures. The plates can stretch out the skin on the face, resulting in the inversion of the eyelids and lips. Typically, affected newborns have an associated flat nose and a missing nasal bridge. The entire outer ear may also be fused to the head by the thick skin, making the ears appear misshapen or missing.

Infants with harlequin ichthyosis can have restrictions in movement of the chest and abdomen leading to respiratory compromise. The hands and feet can be swollen and remain flexed at the joints, resulting in limited mobility. Mortality typically occurs within 2 days of birth due to feeding and breathing complications, and an increased risk of respiratory infections and respiratory distress. Harlequin ichthyosis further predisposes infants to bacterial skin infections (e.g., Staphylococcus aureus), low body temperature, dehydration, and hypernatremia (i.e., elevated sodium levels in the blood) due to a disrupted skin barrier, causing loss of fluid.

Harlequin ichthyosis affects all sexes equally and can occur in several ethnic groups. Currently, the condition affects approximately one in 500,000 births annually in the United States.

How is harlequin ichthyosis diagnosed?

Harlequin ichthyosis is diagnosed at birth on clinical presentation. The Ichthyosis Scoring System (ISS) has been developed to measure global ichthyosis severity in adults and children. It evaluates scale and erythema across various parts of the body. There are ways to diagnose harlequin ichthyosis before birth, including prenatal testing for genetic defects in the ABCA12 gene. In some cases, the associated features may be found on ultrasound during the second or third trimester.

How is harlequin ichthyosis treated?

Harlequin ichthyosis is treated using a multidisciplinary approach focused on symptom management and prevention of infection. Infants are often treated in the intensive care unit and managed for sepsis, electrolyte abnormalities, and temperature dysregulation. Use of a humidified incubator can mitigate water loss and potential issues with thermoregulation. Oral retinoid therapy (e.g., acitretin, oral isotretinoin) has been reported to reduce scaling and expedite shedding of skin. Use of topical emollients and keratolytics (e.g., urea, salicylic acid) can help moisturize the skin and remove scales. Other treatments may target the symptoms that are common in those with ichthyosis, for example inserting a feeding tube to help the infant obtain nutrition, or surgery to manage hand or foot deformities.

What are the most important facts to know about harlequin ichthyosis?

Harlequin ichthyosis is an autosomal recessive genetic condition caused by mutations in ABCA12 that causes thick, scaly plaques of skin that cover the infant’s entire face and body. These plaques can crack and create red fissures across the skin, predisposing to skin infections, cause difficulty breathing and feeding, and result in temperature and electrolyte abnormalities. Harlequin ichthyosis is typically diagnosed on clinical presentation at birth or through genetic testing. Management of harlequin ichthyosis requires a multidisciplinary team to address various complications that may arise. Treatment can include oral retinoids, emollients, and keratolytics.

Key Takeaways

Definition	Harlequin ichthyosis, also known as a harlequin fetus, ichthyosis fetalis, or harlequin baby syndrome, is a condition in which infants are born with thick, hyperkeratotic scales covering their entire body, which can crack and split, leaving large plates of skin with fissures.
Causes	- Mutations in ABCA12 gene → lack of ABC transporter → defects in lipid transport to epidermis and atypical skin barrier → thickened skin - Autosomal recessive inheritance - Both sexes affected equally - 1 in 500,000 births/year in the US
Signs and Symptoms	- Plate-like scales covering the entire body - Scales: transparent, shiny, and taut - Dry out to form plaques separated by red fissures - Inversion of eyelids and lips (as plates stretch out skin on the face) - Flat nose and missing nasal bridge - Outer ear may be fused to the head by the scales - Restriction in chest and abdomen movements → respiratory compromise - Swollen and fixed hands and feet → limited mobility - Predisposition to: bacterial skin infections, low body temperature, dehydration, hypernatremia - Mortality usually within 2 days of birth due to feeding and breathing complications
Diagnosis	- Clinical presentation at birth (Ichthyosis Scoring System) - Prenatal diagnosis: - ABCA12 gene testing - In some cases, features seen on second or third trimester ultrasound
Treatment	- Focus: symptom management and infection prevention - Neonatal intensive care unit - Management of sepsis, electrolyte abnormalities, temperature dysregulation - Oral retinoid therapy - Topical emollients and keratolytics - In some cases: feeding tube, surgery (hand or foot deformities)

References

Akiyama M. Ichthyosis scoring system—a powerful tool in the era of immune pathway–targeted therapies for ichthyosis. JAMA Dermatol. 2022;158(4):354. doi:10.1001/jamadermatol.2021.5342

Digiovanna JJ, Mauro T, Milstone LM, Schmuth M, Toro JR. Systemic retinoids in the management of ichthyoses and related skin types. Dermatol Ther. 2013;26(1):26-38. doi:10.1111/j.1529-8019.2012.01527.x

Harlequin ichthyosis. National Organization for Rare Disorders (NORD). Published July 16, 2019. Accessed September 17, 2025. https://rarediseases.org/rare-diseases/ichthyosis-harlequin-type/

Mazereeuw-Hautier J, Hernández-Martín A, O'Toole EA, et al. Management of congenital ichthyoses: European guidelines of care, part two. Br J Dermatol.2019;180:484.

Zaenglein AL, Levy ML, Stefanko NS, et al. Consensus recommendations for the use of retinoids in ichthyosis and other disorders of cornification in children and adolescents. Pediatr Dermatol. 2021;38:164.