Harlequin type ichthyosis
Encyclopedia
Harlequin-type ichthyosis (also known as "Harlequin baby", Harlequin ichthyosis, ichthyosis congenita, Ichthyosis fetalis, keratosis diffusa fetalis, "Harlequin fetus", and "Ichthyosis congenita gravior"), a skin disease, is the most severe form of congenital ichthyosis
, characterized by a thickening of the keratin
layer in fetal
human skin
. In sufferers of the disease, the skin contains massive, diamond-shaped scales, and tends to have a reddish color. In addition, the eye
s, ear
s, penis
, and the appendages may be abnormally contracted. The scaly keratin greatly limits the child's movement. Because of resultant cracked skin in locations where normal skin would fold, it is easily pregnable by bacteria
and other contaminants, resulting in serious risk of fatal infection.
The harlequin-type designation comes from both the baby's apparent facial expression and the diamond-shape of the scales (resembling the costume of Arlecchino
), which are caused by severe hyperkeratosis
. The disease can be diagnosed
in the uterus
by way of fetal skin biopsy
or by morphologic analysis of amniotic fluid
cells obtained by amniocentesis
. In addition, doctors can now usually recognize common features of the disease through ultrasound
, and follow up with 3D ultrasound to diagnose the condition.
It is associated with a mutation in the gene for the protein ABCA12
.
. The eyelid
s are severely everted (ectropion
), which leaves the eyes and the area around them very susceptible to infection. They often bleed upon birth. The lip
s, pulled by the dry skin, are fixed into a wide grimace (eclabium
). Arms, feet, and fingers are almost always deformed in such a way that they cannot bend properly, and may be below the normal size. They present hypoplasia
in the fingers; therefore, they cannot grab things properly, or they can barely touch them. Polydactyly
, a condition in which one has more than the usual number of toes or fingers, has also been found in these infants.
They are extremely susceptible to changes in temperature
due to their armor-like cracked skin, which prevents normal heat loss. This can result in hyperthermia
. Their respiration
is also restricted by the skin, which impedes the chest wall from expanding and drawing in enough air. This can lead to hypoventilation
and respiratory failure
. Harlequins are often dehydrated, as their plated skin is not well suited to keeping water in.
, infection
(sepsis
), restricted breathing
due to the plating, or other related causes. The most common cause of death was systemic infection and sufferers rarely survived for more than a few days. However, there have been improvements in care, most notably the drug Isotretinoin
(Isotrex). The oldest known survivor is 26-year old Nusrit "Nelly" Shaheen, who is in good health. Lifespan limitations have not yet been determined with the new treatments.
Ichthyosis
Ichthyosis is a heterogeneous family of at least 28, generalized, mostly genetic skin disorders. All types of ichthyosis have dry, thickened, scaly or flaky skin...
, characterized by a thickening of the keratin
Keratin
Keratin refers to a family of fibrous structural proteins. Keratin is the key of structural material making up the outer layer of human skin. It is also the key structural component of hair and nails...
layer in fetal
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
human skin
Human skin
The human skin is the outer covering of the body. In humans, it is the largest organ of the integumentary system. The skin has multiple layers of ectodermal tissue and guards the underlying muscles, bones, ligaments and internal organs. Human skin is similar to that of most other mammals,...
. In sufferers of the disease, the skin contains massive, diamond-shaped scales, and tends to have a reddish color. In addition, the eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
s, ear
Ear
The ear is the organ that detects sound. It not only receives sound, but also aids in balance and body position. The ear is part of the auditory system....
s, penis
Penis
The penis is a biological feature of male animals including both vertebrates and invertebrates...
, and the appendages may be abnormally contracted. The scaly keratin greatly limits the child's movement. Because of resultant cracked skin in locations where normal skin would fold, it is easily pregnable by bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
and other contaminants, resulting in serious risk of fatal infection.
The harlequin-type designation comes from both the baby's apparent facial expression and the diamond-shape of the scales (resembling the costume of Arlecchino
Harlequin
Harlequin or Arlecchino in Italian, Arlequin in French, and Arlequín in Spanish is the most popularly known of the zanni or comic servant characters from the Italian Commedia dell'arte and its descendant, the Harlequinade.-Origins:...
), which are caused by severe hyperkeratosis
Hyperkeratosis
Hyperkeratosis is thickening of the stratum corneum, often associated with a qualitative abnormality of the keratin, and also usually accompanied by an increase also in the granular layer...
. The disease can be diagnosed
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
in the uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
by way of fetal skin biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
or by morphologic analysis of amniotic fluid
Amniotic fluid
Amniotic fluid or liquor amnii is the nourishing and protecting liquid contained by the amniotic sac of a pregnant woman.- Development of amniotic fluid :...
cells obtained by amniocentesis
Amniocentesis
Amniocentesis is a medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal infections, in which a small amount of amniotic fluid, which contains fetal tissues, is sampled from the amnion or amniotic sac surrounding a developing fetus, and the fetal DNA is examined for...
. In addition, doctors can now usually recognize common features of the disease through ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
, and follow up with 3D ultrasound to diagnose the condition.
It is associated with a mutation in the gene for the protein ABCA12
ABCA12
ATP-binding cassette sub-family A member 12 also known as ATP-binding cassette transporter 12 is a protein that in humans is encoded by the ABCA12 gene....
.
Signs and symptoms
The features of the sufferers are severe cranial and facial deformities. The ears may be very poorly developed or absent entirely, as may the noseHuman nose
The visible part of the human nose is the protruding part of the face that bears the nostrils. The shape of the nose is determined by the ethmoid bone and the nasal septum, which consists mostly of cartilage and which separates the nostrils...
. The eyelid
Eyelid
An eyelid is a thin fold of skin that covers and protects an eye. With the exception of the prepuce and the labia minora, it has the thinnest skin of the whole body. The levator palpebrae superioris muscle retracts the eyelid to "open" the eye. This can be either voluntarily or involuntarily...
s are severely everted (ectropion
Ectropion
Ectropion is a medical condition in which the lower eyelid turns outwards. It is one of the notable aspects of newborns exhibiting congenital Harlequin type ichthyosis, but ectropion can occur due to any weakening of tissue of the lower eyelid. The condition can be repaired surgically...
), which leaves the eyes and the area around them very susceptible to infection. They often bleed upon birth. The lip
Lip
Lips are a visible body part at the mouth of humans and many animals. Lips are soft, movable, and serve as the opening for food intake and in the articulation of sound and speech...
s, pulled by the dry skin, are fixed into a wide grimace (eclabium
Eclabium
Eclabium means the turning outwards of a lip. Eclabium comes from the Greek word "ek" meaning "out," and the Latin word "labium" meaning "lip." This deformation occurs in most babies born with Harlequin type ichthyosis....
). Arms, feet, and fingers are almost always deformed in such a way that they cannot bend properly, and may be below the normal size. They present hypoplasia
Hypoplasia
Hypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
in the fingers; therefore, they cannot grab things properly, or they can barely touch them. Polydactyly
Polydactyly
Polydactyly or polydactylism , also known as hyperdactyly, is a congenital physical anomaly in humans, dogs, and cats having supernumerary fingers or toes....
, a condition in which one has more than the usual number of toes or fingers, has also been found in these infants.
They are extremely susceptible to changes in temperature
Temperature
Temperature is a physical property of matter that quantitatively expresses the common notions of hot and cold. Objects of low temperature are cold, while various degrees of higher temperatures are referred to as warm or hot...
due to their armor-like cracked skin, which prevents normal heat loss. This can result in hyperthermia
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...
. Their respiration
Respiratory system
The respiratory system is the anatomical system of an organism that introduces respiratory gases to the interior and performs gas exchange. In humans and other mammals, the anatomical features of the respiratory system include airways, lungs, and the respiratory muscles...
is also restricted by the skin, which impedes the chest wall from expanding and drawing in enough air. This can lead to hypoventilation
Hypoventilation
In medicine, hypoventilation occurs when ventilation is inadequate to perform needed gas exchange...
and respiratory failure
Respiratory failure
The term respiratory failure, in medicine, is used to describe inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges. A drop in blood oxygenation is known as hypoxemia; a rise in arterial...
. Harlequins are often dehydrated, as their plated skin is not well suited to keeping water in.
Treatment and prognosis
In the past, the disorder was always fatal, whether due to dehydrationDehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
, infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
(sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
), restricted breathing
Breathing
Breathing is the process that moves air in and out of the lungs. Aerobic organisms require oxygen to release energy via respiration, in the form of the metabolism of energy-rich molecules such as glucose. Breathing is only one process that delivers oxygen to where it is needed in the body and...
due to the plating, or other related causes. The most common cause of death was systemic infection and sufferers rarely survived for more than a few days. However, there have been improvements in care, most notably the drug Isotretinoin
Isotretinoin
Isotretinoin, INN, is a medication used mostly for cystic acne. It was first developed for brain, pancreatic and other cancers. It is used to treat harlequin-type ichthyosis, a usually lethal skin disease, and lamellar ichthyosis. Its effects are systemic and nonselective...
(Isotrex). The oldest known survivor is 26-year old Nusrit "Nelly" Shaheen, who is in good health. Lifespan limitations have not yet been determined with the new treatments.
History
The disease has been known since 1750, and was first described in the diary of a cleric from Charleston, South Carolina, the Rev. Oliver Hart:"On Thursday, April the 5th, 1750, I went to see a most deplorable object of a child, born the night before of one Mary Evans in 'Chas'town. It was surprising to all who beheld it, and I scarcely know how to describe it. The skin was dry and hard and seemed to be cracked in many places, somewhat resembling the scales of a fish. The mouth was large and round and open. It had no external nose, but two holes where the nose should have been. The eyes appeared to be lumps of coagulated blood, turned out, about the bigness of a plum, ghastly to behold. It had no external ears, but holes where the ears should be. The hands and feet appeared to be swollen, were cramped up and felt quite hard. The back part of the head was much open. It made a strange kind of noise, very low, which I cannot describe. It lived about forty-eight hours and was alive when I saw it."
Notable cases
- Nusrit "Nelly" Shaheen (born 1984) is the oldest survivor with the condition in the UK. She is one of nine children, four of whom also suffered from the condition and died as young children. Nelly lives an active lifestyle and is studying sports coaching and leadership at Hereward College.
- Hunter Steinitz (born 1994) is one of only ten Americans suffering from the disease and is profiled on the National Geographic "Extraordinary Humans: Skin" special.
- Ryan Gonzalez (born 1986) is the oldest person in the United States living with the disease. He was featured in an episode of Medical Incredible.
External links
- A Case Of Harlequin Fetus With Psoriasis In His Family. Article from the Internet Journal of Pediatrics and Neonatology.
- Medical Article from FIRST Foundation
- Profile of 15 year old surviving Harlequin
- Hospital photos and diagrams
- Information from the U.S. National Institutes of HealthNational Institutes of HealthThe National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
- Genetic information