Harlequin-type ichthyosis

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Not to be confused with Harlequin syndrome.
Harlequin type ichthyosis
Classification and external resources
Harlequin fetus.JPG
Harlequin fetus (1886)
ICD-10 Q80.4
ICD-9 757.1
OMIM 242500
DiseasesDB 30052
eMedicine derm/192
MeSH D017490

Harlequin-type ichthyosis (also known as "Harlequin baby",[1] Harlequin ichthyosis,[1] ichthyosis congenita,[1] Ichthyosis fetalis, keratosis diffusa fetalis, "Harlequin fetus",[2]:562 and "Ichthyosis congenita gravior"[1]), 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 eyes, ears, 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.[3]

Signs and symptoms[edit]

The features of the sufferers are severe cranial and facial deformities. The ears may be very poorly developed or absent entirely, as may the nose. The eyelids are severely everted (ectropion), which leaves the eyes and the area around them very susceptible to infection. They often bleed upon birth. The lips, 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 more than the usual number of toes or fingers are present, 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.

Diagnosis[edit]

The diagnosis of harlequin ichthyosis relies on physical examination and certain laboratory examinations including: Physical assessment at birth is vital for the initial diagnosis of Harlequin ichthyosis. Physical examination reveals characteristic symptoms of the condition especially the abnormalities in the skin surface of newborns. Abnormal findings in physical assessments usually result in employing other diagnostic tests to ascertain the diagnosis. Genetic testing is the most specific diagnostic test for harlequin ichthyosis. This test reveals a mutation on the ABCA12 gene. This gene is important in the regulation of protein synthesis for the development of the skin layer. Mutations in the gene may cause impaired transport of lipids in the skin layer and may also lead to shrunken versions of the proteins responsible for skin development. Biopsy of skin may be done to assess the histologic characteristics of the cells. Histological findings usually reveal hyperkeratotic skin cells, which leads to a thick and hard skin layer.

Treatment and prognosis[edit]

In the past, the disorder was always fatal, whether due to dehydration, 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 retinoids such as the drug Isotretinoin (Isotrex). The oldest known survivor is Nusrit "Nelly" Shaheen, who was born in 1984 and is in relatively good health.[4] Lifespan limitations have not yet been determined with the new treatments.

A study published in 2011 in the Archives of Dermatology concluded, "Harlequin ichthyosis should be regarded as a severe chronic disease that is not invariably fatal. With improved neonatal care and probably the early introduction of oral retinoids, the number of survivors is increasing."[5]

History[edit]

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."[6]

Notable cases[edit]

  • Nusrit "Nelly" Shaheen (born 1984) is the oldest known survivor with the condition; she lives in the UK, and was one of nine children. Four of her eight siblings also suffered from the condition but died as young children. Shaheen lives an active lifestyle and in 2008 was studying sports coaching and leadership at Hereward College.[4][7]
  • Hunter Steinitz (born 1994) is one of only twelve Americans suffering from the disease and is profiled on the National Geographic "Extraordinary Humans: Skin" special.[8]
  • Ryan Gonzalez (born 1986)[9] is the oldest person in the United States living with the disease. He was featured in an episode of Medical Incredible.
  • Stephanie Turner (born 1992)[10] is the second oldest person in the United States living with the disease, and the first ever to give birth. Turner's son does not have the disease.

References[edit]

  1. ^ a b c d Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0. 
  2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
  3. ^ Kelsell DP, Norgett EE, Unsworth H, et al. (May 2005). "Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis". Am. J. Hum. Genet. 76 (5): 794–803. doi:10.1086/429844. PMC 1199369. PMID 15756637. 
  4. ^ a b Alison Jones (May 9, 2008). "Nelly is a real diamond girl". Birmingham Post. Retrieved 2008-11-10. 
  5. ^ Rajpopat, S; Moss, C; Mellerio, J; Vahlquist, A; Gånemo, A; Hellstrom-Pigg, M; Ilchyshyn, A; Burrows, N; Lestringant, G; Taylor, A; Kennedy, C; Paige, D; Harper, J; Glover, M; Fleckman, P; Everman, D; Fouani, M; Kayserili, H; Purvis, D; Hobson, E; Chu, C; Mein, C; Kelsell, D; O'Toole, E (June 2011). "Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases.". Archives of dermatology 147 (6): 681–6. doi:10.1001/archdermatol.2011.9. PMID 21339420. 
  6. ^ J. I. Waring, M.D., "Early Mention of a Harlequin Fetus in America", American Journal of Diseases of Children, Vol. 43 No. 2, February 1932
  7. ^ "Harlequin Ichthyosis". Retrieved 2008-11-10. [dead link]
  8. ^ Sean D. Hamill (June 27, 2010). "City girl aims to educate about her skin disease". Pittsburgh Post-Gazette. Retrieved 2010-06-27. 
  9. ^ Man Survives Rare Skin-Shedding Disease: Harlequin Ichthyosis Usually Fatal At Birth, 10News.com San Diego; posted November 16, 2004; backup at WayBack Machine
  10. ^ Mid-South woman with rare genetic condition defies odds, deliverers healthy baby, by Ursula Madden; at Fox19 Cincinnati; posted Aug 26, 2013; retrieved Aug 27, 2013

Further reading[edit]

  • Akiyama M (1999). "The pathogenesis of severe congenital ichthyosis of the neonate". J Dermatol Sci. 21 (2): 96–104. doi:10.1016/S0923-1811(99)00024-9. PMID 10511478. 
  • Moskowitz DG, Fowler AJ, Heyman MB, et al. (2004). "Pathophysiologic basis for growth failure in children with ichthyosis: an evaluation of cutaneous ultrastructure, epidermal permeability barrier function, and energy expenditure". J Pediatr. 145 (1): 82–92. doi:10.1016/j.jpeds.2004.03.052. PMID 15238912. 

External links[edit]