National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Harlequin ichthyosis


Other Names:
Ichthyosis congenita, Harlequin fetus type; Harlequin fetus
Categories:
Harlequin ichthyosis is a severe genetic disorder that mainly affects the skin.[1] The newborn infant is covered with plates of thick skin that crack and split apart. The thick plates can pull at and distort facial features and can restrict breathing and eating.[2] Mutations in the ABCA12 gene cause harlequin ichthyosis.[1] This condition is inherited in an autosomal recessive pattern.[1][2] 
Last updated: 2/6/2015

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 23 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Congenital ichthyosiform erythroderma 0007431
Depressed nasal ridge
Flat nose
Recessed nasal ridge
[ more ] 		0000457
Ectropion
Eyelid turned out
0000656
Hearing abnormality
Abnormal hearing
0000364
Hyperkeratosis 0000962
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ] 		0002205
30%-79% of people have these symptoms
Eclabion
Outward turned lips
0012472
Erythroderma 0001019
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion
[ more ] 		0001376
5%-29% of people have these symptoms
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Dehydration 0001944
Foot polydactyly
Duplication of bones of the toes
0001829
Hand polydactyly
Extra finger
0001161
Malignant hyperthermia 0002047
Respiratory insufficiency
Respiratory impairment
0002093
Self-injurious behavior
Self-injurious behaviour
0100716
Sudden cardiac death
Premature sudden cardiac death
0001645
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance 0000007
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip
[ more ] 		0000232
Premature birth
Premature delivery of affected infants
Preterm delivery
[ more ] 		0001622
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes
[ more ] 		0000520
Rigidity
Muscle rigidity
0002063
Short finger
Stubby finger
0009381
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Last updated: 7/1/2020
Harlequin ichthyosis is caused by mutations in the ABCA12 gene. This gene provides instructions for making a protein that is essential for the normal development of skin cells. This protein plays a major role in the transport of fats (lipids) in the outermost layer of skin (the epidermis). Some mutations in the ABCA12 gene prevent the cell from making any ABCA12 protein, while others lead to the production of an abnormally small version of the protein that cannot transport lipids properly. A loss of functional ABCA12 protein disrupts the normal development of the epidermis, resulting in the hard, thick scales characteristic of harlequin ichthyosis.[1]
Last updated: 2/9/2015
Harlequin ichthyosis is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.[1]
Last updated: 2/9/2015
Yes, harlequin ichthyosis can be diagnosed before birth using either amniocentesis or chorionic villus sampling. Both of these procedures are used to obtain a sample of fetal DNA, which can be tested for mutations in the ABCA12 gene. The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a specific genetic test should contact a health care provider or a genetics professional.  
Last updated: 2/6/2015

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
HI may be confused with the less severe appearance of collodion baby. Later in life, the differential diagnosis includes congenital ichthyosiform erythroderma (CIE), lethal restrictive dermopathy, infantile systemic hyalinosis, and Neu-Laxova syndrome (see these terms).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Harlequin ichthyosis. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Harlequin ichthyosis. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Harlequin ichthyosis:
    The National Registry for Ichthyosis & Related Skin Disorders
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Harlequin ichthyosis. This website is maintained by the National Library of Medicine.
  • DermNetNZ provides information on ichthyosis in general. DermNetNZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
  • A Positive Exposure program called FRAME has an educational film about ichthyosis that was created to change how medical information is presented to healthcare professionals. FRAME stands for Faces Redefining the Art of Medical Education. Positive Exposure is an organization that uses photography, film, and narrative to transform public perceptions of people living with genetic, physical, intellectual, and behavioral differences.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Harlequin ichthyosis. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • Can Harlequin ichthyosis be diagnosed before birth? Specifically, can it be diagnosed by amniocentesis or chorionic villus sampling (CVS)? See answer


  1. Harlequin ichthyosis. Genetics Home Reference (GHR). November 2008; http://ghr.nlm.nih.gov/condition=harlequinichthyosis. Accessed 2/6/2015.
  2. Ichthyosis, Harlequin Type. National Organization for Rare Disorders (NORD). 2006; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/546/viewAbstract. Accessed 2/6/2015.