harlequin fetus

道化師様胎児

WordNet

1. variegate with spots or marks; "His face was harlequined with patches"
2. a clown or buffoon (after the Harlequin character in the commedia dellarte)
3. an unborn or unhatched vertebrate in the later stages of development showing the main recognizable features of the mature animal (同)foetus

PrepTutorEJDIC

1. 《H-》ハーレクィン,アルカン(無言劇などの道化役) / 〈C〉道化師,道化もの

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2019/07/01 07:22:18」(JST)

wiki en

[Wiki en表示]

Not to be confused with Harlequin syndrome.

Harlequin-type ichthyosis
Other names	Harlequin ichthyosis, hyosis fetalis, keratosis diffusa fetalis, harlequin fetus, ichthyosis congenita gravior
Harlequin fetus (1886)
Specialty	Dermatology
Symptoms	Very thick skin which cracks, abnormal facial features
Complications	Breathing problems, infection, problems with body temperature, dehydration
Usual onset	Present from birth
Causes	Genetic (autosomal recessive)
Diagnostic method	Based on appearance and genetic testing
Differential diagnosis	Ichthyosis congenita, Lamellar ichthyosis
Treatment	Supportive care, moisturizing cream
Medication	Antibiotics, etretinate, retinoids
Prognosis	Death in the first month is relatively common
Frequency	1 in 300,000

Harlequin-type ichthyosis is a genetic disorder which results in thickened skin over nearly the entire body at birth. The skin forms large, diamond-shaped plates that are separated by deep cracks. They affect the shape of the eyelids, nose, mouth, and ears, and limit movement of the arms and legs. Restricted movement of the chest can lead to breathing difficulties. These plates fall off over several weeks. Other complications can include premature birth, infection, problems with body temperature, and dehydration.

Harlequin-type ichthyosis is due to mutations of the ABCA12 genes. It is autosomal recessive, and inherited from a person's parents. Diagnosis is often based on appearance at birth and confirmed by genetic testing. Before birth amniocentesis or ultrasound may support the diagnosis.

There is no cure. Early in life constant supportive care is typically required. Treatments may include moisturizing cream, antibiotics, etretinate, or retinoids. It affects about 1 per 300,000 births. Both sexes are affected equally commonly. Long term problems are common. Death in the first month is relatively common. The condition was first documented in 1750.

Signs and symptoms

Newborns with harlequin-type ichthyosis present with thick, fissured armor-plate hyperkeratosis. 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. In addition, the fish mouth appearance, mouth breathing, and xerostomia place affected individuals at extremely high risk for developing rampant dental decay.

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. Patients 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 loss of function 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. Less severe mutations result in a collodion membrane and congenital ichthyosiform erythroderma-like presentation. ABCA12 is an ATP binding cassette (ABC) transporter, and is a member of a large family of proteins that hydrolyze ATP to transport cargo across membranes. ABCA12 is thought to be a lipid transporter in keratinocytes necessary for lipid transport into lamellar granules during the formation of the lipid barrier. 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, white and hard skin layer.

Treatment and prognosis

Constant care is required to moisturize and protect the skin. The hard outer layer eventually peels off, leaving the vulnerable inner layers of the dermis exposed. Early complications result from infection due to fissuring of the hyperkeratotic plates and respiratory distress due to physical restriction of chest wall expansion. Management includes supportive care and treatment of hyperkeratosis and skin barrier dysfunction. A humidified incubator is generally used. Intubation is often required until nares are patent. Nutritional support with tube feeds is essential until eclabium resolves and infants can begin nursing. Ophthalmology consultation is useful for the early management of ectropion, which is initially pronounced and resolves as scales are shed. Liberal application of petrolatum is needed multiple times a day. In addition, careful debridement of constrictive bands of hyperkeratosis should be performed to avoid digital ischemia. Cases of digital autoamputation or necrosis have been reported due to cutaneous constriction bands. Relaxation incisions have been used to prevent this morbid complication.

In the past, the disorder was nearly 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, improved neonatal intensive care and early treatment with oral retinoids, such as the drug Isotretinoin (Isotrex), may improve survival. Early oral retinoid therapy has been shown to soften scales and encourage desquamation. After as little as two weeks of daily oral isotretinoin, fissures in the skin can heal, and plate-like scales can nearly resolve. Improvement in the eclabium and ectropion can also be seen in a matter of weeks. Children who survive the neonatal period usually evolve to a less severe phenotype, resembling a severe congenital ichthyosiform erythroderma. Patients continue to suffer from temperature disregulation and may have heat and cold intolerance. Patients can also have generalized poor hair growth, scarring alopecia, contractures of digits, arthralgias, failure to thrive, hypothyroidism, and short stature. Some patients develop a rheumatoid factor-positive polyarthritis. Survivors can also develop fish-like scales and retention of a waxy, yellowish material in seborrheic areas, with ear adhered to the scalp.

The oldest known survivor is Nusrit "Nelly" Shaheen, who was born in 1984 and is in relatively good health as of March 2017. The maximum lifespan of patients with this disease has 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."

History

The disease has been known since 1750, and was first described in the diary of Rev. Oliver Hart from Charleston, South Carolina:

"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."

The harlequin-type designation comes from the diamond shape of the scales at birth (resembling the costume of Arlecchino).

Notable cases

• A case reported in Bermuda (female born in 1974) is likely the eldest known survivor.
• Nusrit "Nelly" Shaheen (born in 1984) is possibly the oldest known survivor in England; 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.
• Hunter Steinitz (born October 17, 1994) is one of only twelve Americans living with the disease and is profiled on the National Geographic "Extraordinary Humans: Skin" special.
• Ryan Gonzalez (born in 1986) is the oldest person in the United States living with the disease. He was featured in an episode of Medical Incredible.
• Stephanie Turner (1993 – 2017) was 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. She died on March 3, 2017, at age 23.
• 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. 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.
• Mui Thomas (born in 1992 in Hong Kong) qualified as first rugby referee with harlequin ichthyosis.
• A female baby born in Nagpur, India in June 2016 died after two days. She is reported as the first case in India.
• What is believed to be the second case in India was reported in January 2017 in Patna, the capital of Bihar. Deputy superintendent of Paliganj sub-divisional hospital Dr Shiv Lal Chaudhary, who is also in charge of Paliganj PHC, said the baby was born through a normal delivery. The baby was born four weeks prematurely. The couple's other child, aged 18 months, is not reported to have the disease.
• The third child in India born with the harlequin ichthyosis in Delhi at Kasturba Gandhi Hospital to a 20 year old Muslim woman. The child died after developing respiratory problems.

External links

Classification	D ICD-10: Q80.4 ICD-9-CM: 757.1 OMIM: 242500 MeSH: D017490 DiseasesDB: 30052
External resources	eMedicine: derm/192 Orphanet: 457

• Information from the U.S. National Institutes of Health

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 遺伝性の魚鱗癬の概要 overview of the inherited ichthyoses
• 2. 新生児および乳児における皮膚および頭皮の良性病変 benign skin and scalp lesions in the newborn and young infant
• 3. 遺伝性皮膚症 the genodermatoses
• 4. 新生児および乳児の紅皮症 neonatal and infantile erythroderma

English Journal

• Novel mutation in NIPAL4 in a Romanian family with autosomal recessive congenital ichthyosis.

• Maier D1, Mazereeuw-Hautier J2,3, Tilinca M4, Cosgarea R1, Jonca N3.
• Clinical and experimental dermatology.Clin Exp Dermatol.2016 Apr;41(3):279-82. doi: 10.1111/ced.12740. Epub 2015 Oct 12.
• Autosomal recessive congenital ichthyosis (ARCI), a severe and highly clinically heterogeneous group of mendelian disorders of cornification, is the result of mutations in at least nine genes regulating the epidermal barrier functionality. NIPAL4 is the second most frequently mutated ARCI gene. We r
• PMID 26456858

• Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia: Clinical Characteristics and Novel and Recurrent Mutations in 132 Patients.

• Hellström Pigg M1, Bygum A, Gånemo A, Virtanen M, Brandrup F, Zimmer AD, Hotz A, Vahlquist A, Fischer J.
• Acta dermato-venereologica.Acta Derm Venereol.2016 Mar 30. doi: 10.2340/00015555-2418. [Epub ahead of print]
• Autosomal recessive congenital ichthyosis (ARCI) represents a heterogeneous group of rare disorders of cornification with 3 major subtypes: harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). A 4th subtype has also been proposed: pleomorphic ichthyosi
• PMID 27025581

• Inherited ichthyosis: Non-syndromic forms.

• Takeichi T1, Akiyama M1.
• The Journal of dermatology.J Dermatol.2016 Mar;43(3):242-51. doi: 10.1111/1346-8138.13243.
• Inherited ichthyoses are a group of genetic disorders characterized by generalized dry skin, scaling and hyperkeratosis, and often associated with erythroderma. These manifestations are due to mutations in genes mostly involved in skin barrier formation. Inherited ichthyoses consist of non-syndromic
• PMID 26945532

Japanese Journal

• 先天異常の出生前診断 : その現況と問題点

• 日本産科婦人科學會雜誌 = Acta obstetrica et gynaecologica Japonica 40(8), 1027-1032, 1988-08-01
• NAID 110002224184

• Harlequin fetus diagnosed by fetal skin biopsy

• Clinical Dermatology, The CMD Cases Collection, 5-6, 1987
• NAID 10007727585

• 41.Harlequin fetus の1例(第19回日本小児外科学会東海地方会)

• 日本小児外科学会雑誌 22(7), 1303-1304, 1986
• NAID 110002098027

Related Links

• 魚鱗癬 - Wikipedia

[編集] 葉状魚鱗癬. ［ようじょう ぎょりんせん］: 常染色体劣性遺伝形式をとる。生まれた ときより発症する。生まれたとき、菱形にめくれた皮膚が道化師風であるため、「道化師 様胎児（collodion baby、Harlequin disease)」と呼ばれることがある。

---

★リンクテーブル★

リンク元	「道化師様胎児」
関連記事	「harlequin」

「道化師様胎児」

　　[★]

英

harlequin fetus

同

道化師様魚鱗癬 harlequin ichthyosis

「harlequin」

　　[★]

• n.

• (喜劇などの)道化役、ひょうきん者

• adj.

• まだら（模様）の

• vt.

• まだらにする