Not to be confused with Harlequin syndrome.
|
|
This article needs more medical references for verification or relies too heavily on primary sources, specifically: Information on page does not cite enough references or sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed. (February 2015) |
|
| Harlequin-type ichthyosis |
|
Harlequin fetus (1886)
|
| Classification and external resources |
| Specialty |
Dermatology |
| ICD-10 |
Q80.4 |
| ICD-9-CM |
757.1 |
| OMIM |
242500 |
| DiseasesDB |
30052 |
| eMedicine |
derm/192 |
| MeSH |
D017490 |
| Orphanet |
457 |
|
[edit on Wikidata]
|
Harlequin-type ichthyosis (also known as harlequin baby,[1] harlequin ichthyosis,[1] hyosis fetalis, keratosis diffusa fetalis, harlequin fetus,[2]:562 and ichthyosis congenita gravior[1]), is a severe genetic skin disease, which causes thickening of the stratum corneum of the epidermis.[3] At birth, the child’s whole body is encased in an 'armour' of thick white plates of skin, separated with deep cracks. In addition, the eyes, ears, penis, and the appendages may be abnormally contracted. Because of resultant cracked skin in locations where normal skin would fold, it is easily pregnable by bacteria and other contaminants, which can result in serious risk of fatal infection. Constant care is required to moisturise and protect the skin.[4]
The harlequin-type designation comes from the diamond shape of the scales at birth (resembling the costume of Arlecchino), 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. 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.[5]
Contents
- 1 Signs and symptoms
- 2 Diagnosis
- 3 Treatment and prognosis
- 4 History
- 5 Notable cases
- 6 References
- 7 Further reading
- 8 External links
Signs and symptoms
Sufferers feature severe cranial and facial deformities. The ears may be very poorly developed or absent entirely, as may the nose. The eyelids may be everted (ectropion), which leaves the eyes and the area around them very susceptible to infection. Babies with this condition often bleed during birth. The lips are pulled back by the dry skin (eclabium). Joints are sometimes lacking in movement, and may be below the normal size. Hypoplasia is sometimes found in the fingers. Polydactyly has also been found on occasion.
Patients with this condition are extremely sensitive to changes in temperature due to their hard cracked skin, which prevents normal heat loss. 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 retaining water.
Diagnosis
The diagnosis of Harlequin-type Ichthyosis relies on both physical examination and certain laboratory tests. 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
Constant care is required to moisturise and protect the skin. The hard outer layer eventually peels off, leaving the vulnerable inner layers of the dermis exposed. 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 as of May 9, 2008.[6] 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."[7]
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."[8]
Notable cases
- Nusrit "Nelly" Shaheen (born 1984) is the oldest known survivor with the condition; she resides in Coventry, and was one of nine children in a Pakistani Muslim household. Four of her eight siblings also had the condition but died as young children. Shaheen lives an active lifestyle and in 2008 was studying sports coaching and leadership at Hereward College.[6][9]
- Hunter Steinitz (born 1994) is one of only twelve Americans living with the disease and is profiled on the National Geographic "Extraordinary Humans: Skin" special.[10]
- Ryan Gonzalez (born 1986)[11] 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)[12] is the second oldest person in the United States living with the disease, and the first ever to give birth. Turner's two children do not have the disease.[13]
- Mason van Dyke, despite being given a life expectancy of one to five days, was 21 months old and active, as of December 31, 2014.[14] Doctors told his mother Lisa van Dyke that he was the first case of Harlequin Ichthyosis in South Africa, and that she has a one-in-four chance to have another child with the disease.
References
- ^ a b c Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
- ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
- ^ http://www.ncbi.nlm.nih.gov/pubmed/25857373
- ^ "Harlequin Ichthyosis". http://www.shhirt.org.uk. Retrieved 18 February 2015.
- ^ 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.
- ^ a b Alison Jones (May 9, 2008). "Nelly is a real diamond girl". Birmingham Post. Retrieved 2008-11-10.
- ^ 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.
- ^ 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
- ^ "Harlequin Ichthyosis". Archived from the original on October 14, 2008. Retrieved 2008-11-10.
- ^ Sean D. Hamill (June 27, 2010). "City girl aims to educate about her skin disease". Pittsburgh Post-Gazette. Retrieved 2010-06-27.
- ^ Man Survives Rare Skin-Shedding Disease: Harlequin Ichthyosis Usually Fatal At Birth, 10News.com San Diego; posted November 16, 2004; backup at WayBack Machine
- ^ 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
- ^ 'People ask me if I've been in a fire', says mother, 23, with rare condition which causes her skin to grow seven times faster than normal, Daily Mail, 2 December 2015
- ^ News24 (Dec 31, 2014). "21-month-old boy defies the odds, thrives living with Harlequin Ichthyosis". News24. Retrieved 2015-01-01.
Further reading
- 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
- A Case Of Harlequin Fetus With Psoriasis In His Family. Article from the Internet Journal of Pediatrics and Neonatology.
- Medical Article Harlequin Ichthyosis article from Foundation for Ichthyosis and Related Skin Types
- Profile of 15-year-old surviving Harlequin
- Hospital photos and diagrams
- Information from the U.S. National Institutes of Health
- Genetic information
- Foundation for Ichthyosis Research in MONACO
|
Genetic disorder, membrane: ABC-transporter disorders
|
|
| ABCA |
- ABCA1 (Tangier disease)
- ABCA3 (Surfactant metabolism dysfunction 3)
- ABCA4 (Stargardt disease 1, Retinitis pigmentosa 19)
- ABCA12 (Harlequin-type ichthyosis, Lamellar ichthyosis 2)
|
|
| ABCB |
- ABCB4 (Progressive familial intrahepatic cholestasis 3)
- ABCB7 (ASAT)
- ABCB11 (Progressive familial intrahepatic cholestasis 2)
|
|
| ABCC |
- ABCC2 (Dubin–Johnson syndrome)
- ABCC6 (Pseudoxanthoma elasticum)
- ABCC7 (Cystic fibrosis)
- ABCC8 (HHF1, TNDM2)
- ABCC9 (Dilated cardiomyopathy 1O)
|
|
| ABCD |
- ABCD1 (Adrenoleukodystrophy, Adrenomyeloneuropathy)
|
|
| ABCG |
- ABCG5 (Sitosterolemia)
- ABCG8 (Gallbladder disease 4, Sitosterolemia)
|
|
|
see also ABC transporters
|
Index of cells
|
|
| Description |
- Structure
- Organelles
- peroxisome
- cytoskeleton
- centrosome
- epithelia
- cilia
- mitochondria
- Membranes
- Membrane transport
- ion channels
- vesicular transport
- solute carrier
- ABC transporters
- ATPase
- oxidoreduction-driven
|
|
| Disease |
- Structural
- peroxisome
- cytoskeleton
- cilia
- mitochondria
- nucleus
- scleroprotein
- Membrane
- channelopathy
- solute carrier
- ATPase
- ABC transporters
- other
- extracellular ligands
- cell surface receptors
- intracellular signalling
- Vesicular transport
- Pore-forming toxins
|
|
|
