Rare Neurology News

Disease Profile

Harlequin ichthyosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

Q80.4

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Ichthyosis congenita, Harlequin fetus type; Harlequin fetus

Categories

Congenital and Genetic Diseases; Skin Diseases

Summary

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]

Symptoms

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.

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

Cause

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]

Diagnosis

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.

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.

    Organizations

    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

      Learn more

      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

      • DermNetNZ provides information on ichthyosis in general. DermNetNZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated.
      • Genetics Home Reference (GHR) contains information on Harlequin ichthyosis. This website is maintained by the National Library of Medicine.
      • 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.

          References

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

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