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Autosomal recessive congenital ichthyosis 6(ARCI6)

MedGen UID:
436851
Concept ID:
C2677065
Disease or Syndrome
Synonym: ARCI6
 
Gene (location): NIPAL4 (5q33.3)
 
Monarch Initiative: MONDO:0012847
OMIM®: 612281

Authors:
Gabriele Richard   view full author information

Additional descriptions

From GeneReviews Overview
Autosomal recessive congenital ichthyosis (ARCI) encompasses several forms of nonsyndromic ichthyosis. Although most neonates with ARCI are collodion babies, the clinical presentation and severity of ARCI may vary significantly, ranging from harlequin ichthyosis, the most severe and often fatal form, to lamellar ichthyosis (LI) and (nonbullous) congenital ichthyosiform erythroderma (CIE). These phenotypes are now recognized to fall on a continuum; however, the phenotypic descriptions are clinically useful for clarification of prognosis and management. Infants with harlequin ichthyosis are usually born prematurely and are encased in thick, hard, armor-like plates of cornified skin that severely restrict movement. Life-threatening complications in the immediate postnatal period include respiratory distress, feeding problems, and systemic infection. Collodion babies are born with a taut, shiny, translucent or opaque membrane that encases the entire body and lasts for days to weeks. LI and CIE are seemingly distinct phenotypes: classic, severe LI with dark brown, plate-like scale with no erythroderma and CIE with finer whiter scale and underlying generalized redness of the skin. Affected individuals with severe involvement can have ectropion, eclabium, scarring alopecia involving the scalp and eyebrows, and palmar and plantar keratoderma. Besides these major forms of nonsyndromic ichthyosis, a few rare subtypes have been recognized, such as bathing suit ichthyosis, self-improving collodion ichthyosis, or ichthyosis-prematurity syndrome.
From OMIM
Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010). NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006). In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005). For a general phenotypic description and discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300).  http://www.omim.org/entry/612281
From MedlinePlus Genetics
Nonbullous congenital ichthyosiform erythroderma (NBCIE) is a condition that mainly affects the skin. Many infants with this condition are born with a tight, clear sheath covering their skin called a collodion membrane. Constriction by the membrane may cause the lips and eyelids to be turned out so the inner surface is exposed. The collodion membrane is usually shed during the first few weeks of life. Following shedding of the collodion membrane, the skin is red (erythroderma) and covered with fine, white scales (ichthyosis). Infants with NBCIE may develop infections, an excessive loss of fluids (dehydration), and respiratory problems early in life.

In individuals with NBCIE, some of the skin problems may improve by adulthood. Life expectancy is normal in people with NBCIE.

Some people with NBCIE have thickening of the skin on the palms of the hands and soles of the feet (palmoplantar keratoderma), decreased or absent sweating (anhidrosis), and abnormal nails (nail dystrophy). In severe cases, there is an absence of hair growth (alopecia) in certain areas, often affecting the scalp and eyebrows.  https://medlineplus.gov/genetics/condition/nonbullous-congenital-ichthyosiform-erythroderma

Clinical features

From HPO
Palmoplantar keratoderma
MedGen UID:
1635750
Concept ID:
C4551675
Disease or Syndrome
Abnormal thickening of the skin of the palms of the hands and the soles of the feet.
Erythroderma
MedGen UID:
3767
Concept ID:
C0011606
Disease or Syndrome
An inflammatory exfoliative dermatosis involving nearly all of the surface of the skin. Erythroderma develops suddenly. A patchy erythema may generalize and spread to affect most of the skin. Scaling may appear in 2-6 days and be accompanied by hot, red, dry skin, malaise, and fever.
Ectropion
MedGen UID:
4448
Concept ID:
C0013592
Disease or Syndrome
An outward turning (eversion) or rotation of the eyelid margin.
Hypohidrosis
MedGen UID:
43796
Concept ID:
C0020620
Disease or Syndrome
Abnormally diminished capacity to sweat.
Parakeratosis
MedGen UID:
10572
Concept ID:
C0030436
Disease or Syndrome
Abnormal formation of the keratinocytes of the epidermis characterized by persistence of nuclei, incomplete formation of keratin, and moistness and swelling of the keratinocytes.
Congenital nonbullous ichthyosiform erythroderma
MedGen UID:
38180
Concept ID:
C0079154
Disease or Syndrome
The term collodion baby applies to newborns who appear to have an extra layer of skin (known as a collodion membrane) that has a collodion-like quality. It is a descriptive term, not a specific diagnosis or disorder (as such, it is a syndrome). Affected babies are born in a collodion membrane, a shiny waxy outer layer to the skin. This is shed 10-14 days after birth, revealing the main symptom of the disease, extensive scaling of the skin caused by hyperkeratosis. With increasing age, the scaling tends to be concentrated around joints in areas such as the groin, the armpits, the inside of the elbow and the neck. The scales often tile the skin and may resemble fish scales.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.
Epidermal acanthosis
MedGen UID:
65136
Concept ID:
C0221270
Finding
Diffuse hypertrophy or thickening of the stratum spinosum of the epidermis (prickle cell layer of the skin).
Scaling skin
MedGen UID:
472970
Concept ID:
C0237849
Finding
Refers to the loss of the outer layer of the epidermis in large, scale-like flakes.
Hyperkeratosis
MedGen UID:
209030
Concept ID:
C0870082
Disease or Syndrome
Hyperkeratosis is thickening of the outer layer of the skin, the stratum corneum, which is composed of large, polyhedral, plate-like envelopes filled with keratin which are the dead cells that have migrated up from the stratum granulosum.
Orthokeratosis
MedGen UID:
375169
Concept ID:
C1843359
Finding
Formation of an anuclear keratin layer
Generalized ichthyosis
MedGen UID:
765442
Concept ID:
C3552528
Finding

Professional guidelines

PubMed

Clabbers J, van Oosten NV, Bolling M, Vreeburg M, van Geel M, Steijlen P, Gostynski A
Dermatology 2024;240(1):170-177. Epub 2023 Sep 4 doi: 10.1159/000533934. PMID: 37666225
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Pediatr Dermatol 2022 May;39(3):420-424. Epub 2022 Apr 12 doi: 10.1111/pde.14944. PMID: 35412663
Lucker GP, Steijen PM, Suykerbuyk EJ, Kragballe K, Brandrup F, van de Kerkhof PC
Acta Derm Venereol 1996 Mar;76(2):97-101. doi: 10.2340/000155557697101. PMID: 8740259

Recent clinical studies

Etiology

Supsrisunjai C, Bunnag T, Chaowalit P, Boonpuen N, Kootiratrakarn T, Wessagowit V
Pediatr Dermatol 2023 Jan;40(1):107-112. Epub 2022 Oct 19 doi: 10.1111/pde.15156. PMID: 36262015
Zaouak A, Chamli A, Ben Mansour N, Jouini W, Fenniche S, Hammami H
Clin Dermatol 2022 Jul-Aug;40(4):388-394. Epub 2022 Feb 15 doi: 10.1016/j.clindermatol.2022.02.012. PMID: 35181410
Mohamad J, Samuelov L, Malchin N, Rabinowitz T, Assaf S, Malki L, Malovitski K, Israeli S, Grafi-Cohen M, Bitterman-Deutsch O, Molho-Pessach V, Cohen-Barak E, Bach G, Garty BZ, Bergman R, Harel A, Nanda A, Lestringant GG, McGrath J, Shalev S, Shomron N, Mashiah J, Eskin-Schwartz M, Sprecher E, Sarig O
Exp Dermatol 2021 Sep;30(9):1290-1297. Epub 2021 Apr 15 doi: 10.1111/exd.14345. PMID: 33786896
Heinz L, Kim GJ, Marrakchi S, Christiansen J, Turki H, Rauschendorf MA, Lathrop M, Hausser I, Zimmer AD, Fischer J
Am J Hum Genet 2017 Jun 1;100(6):926-939. doi: 10.1016/j.ajhg.2017.05.007. PMID: 28575648Free PMC Article
Rodríguez-Pazos L, Ginarte M, Vega A, Toribio J
Actas Dermosifiliogr 2013 May;104(4):270-84. Epub 2013 Apr 3 doi: 10.1016/j.adengl.2011.11.021. PMID: 23562412

Diagnosis

Supsrisunjai C, Bunnag T, Chaowalit P, Boonpuen N, Kootiratrakarn T, Wessagowit V
Pediatr Dermatol 2023 Jan;40(1):107-112. Epub 2022 Oct 19 doi: 10.1111/pde.15156. PMID: 36262015
Chiramel MJ, Mathew L, Athirayath R, Chapla A, Sathishkumar D, Mani T, Danda S, George R
Pediatr Dermatol 2022 May;39(3):420-424. Epub 2022 Apr 12 doi: 10.1111/pde.14944. PMID: 35412663
Zaouak A, Chamli A, Ben Mansour N, Jouini W, Fenniche S, Hammami H
Clin Dermatol 2022 Jul-Aug;40(4):388-394. Epub 2022 Feb 15 doi: 10.1016/j.clindermatol.2022.02.012. PMID: 35181410
Rodríguez-Pazos L, Ginarte M, Vega A, Toribio J
Actas Dermosifiliogr 2013 May;104(4):270-84. Epub 2013 Apr 3 doi: 10.1016/j.adengl.2011.11.021. PMID: 23562412
Victor F, Schaffer JV
Dermatol Online J 2005 Dec 30;11(4):13. PMID: 16403385

Therapy

Murrell DF, Teng JMC, Guenthner S, Marathe K, Kempers S, Eads K, Castelo-Soccio L, Mendelsohn AM, Raiz J, Bunick CG
Clin Exp Dermatol 2023 Jun 5;48(6):623-630. doi: 10.1093/ced/llad033. PMID: 36794376
Teng JMC, Bunick CG, Guenthner S, Murrell DF, Marathe K, Kempers S, Eads K, Mendelsohn AM, Raiz J, Tavakkol A, Castelo-Soccio L
J Am Acad Dermatol 2022 Dec;87(6):1455-1458. Epub 2022 Jul 21 doi: 10.1016/j.jaad.2022.07.028. PMID: 35872261
Khalili A, Schear M, Greaves G, Schwartzstein HR, Kodsi S, Gorski M
J AAPOS 2019 Dec;23(6):352-354. Epub 2019 Oct 3 doi: 10.1016/j.jaapos.2019.08.274. PMID: 31586585
Sethuraman G, Marwaha RK, Challa A, Yenamandra VK, Ramakrishnan L, Thulkar S, Sharma VK
Pediatrics 2016 Jan;137(1) Epub 2015 Dec 31 doi: 10.1542/peds.2015-1313. PMID: 26721572
Renner ED, Hartl D, Rylaarsdam S, Young ML, Monaco-Shawver L, Kleiner G, Markert ML, Stiehm ER, Belohradsky BH, Upton MP, Torgerson TR, Orange JS, Ochs HD
J Allergy Clin Immunol 2009 Sep;124(3):536-43. Epub 2009 Aug 14 doi: 10.1016/j.jaci.2009.06.009. PMID: 19683336Free PMC Article

Prognosis

Serra G, Memo L, Cavicchioli P, Cutrone M, Giuffrè M, La Torre ML, Schierz IAM, Corsello G
Ital J Pediatr 2022 Aug 13;48(1):145. doi: 10.1186/s13052-022-01336-0. PMID: 35964051Free PMC Article
Gruber R, Rainer G, Weiss A, Udvardi A, Thiele H, Eckl KM, Schupart R, Nürnberg P, Zschocke J, Schmuth M, Volc-Platzer B, Hennies HC
Br J Dermatol 2017 Apr;176(4):1068-1073. Epub 2017 Jan 17 doi: 10.1111/bjd.14860. PMID: 27449533
Wakil SM, Binamer Y, Al-Dossari H, Al-Humaidy R, Thuraya RA, Khalifa O, Finsterer J, Meyer BF, Al Owain M
Int J Dermatol 2016 Jun;55(6):673-9. Epub 2016 Apr 7 doi: 10.1111/ijd.13279. PMID: 27061915
Chen YW, Wang JK, Chou FP, Wu BY, Hsiao HC, Chiu H, Xu Z, Baksh ANH, Shi G, Kaul M, Barndt R, Shanmugam VK, Johnson MD, Lin CY
J Invest Dermatol 2014 Feb;134(2):405-414. Epub 2013 Jul 26 doi: 10.1038/jid.2013.320. PMID: 23900022Free PMC Article
Williams ML, Elias PM
Arch Dermatol 1985 Apr;121(4):477-88. doi: 10.1001/archderm.121.4.477. PMID: 3977371

Clinical prediction guides

Murrell DF, Teng JMC, Guenthner S, Marathe K, Kempers S, Eads K, Castelo-Soccio L, Mendelsohn AM, Raiz J, Bunick CG
Clin Exp Dermatol 2023 Jun 5;48(6):623-630. doi: 10.1093/ced/llad033. PMID: 36794376
Abeni D, Rotunno R, Diociaiuti A, Giancristoforo S, Bonamonte D, Filoni A, Schepis C, Siragusa M, Neri I, Virdi A, Castiglia D, Zambruno G, Bodemer C, El Hachem M
Acta Derm Venereol 2021 Jun 22;101(6):adv00477. doi: 10.2340/00015555-3822. PMID: 33954798Free PMC Article
Paller AS, Renert-Yuval Y, Suprun M, Esaki H, Oliva M, Huynh TN, Ungar B, Kunjravia N, Friedland R, Peng X, Zheng X, Estrada YD, Krueger JG, Choate KA, Suárez-Fariñas M, Guttman-Yassky E
J Allergy Clin Immunol 2017 Jan;139(1):152-165. Epub 2016 Aug 20 doi: 10.1016/j.jaci.2016.07.019. PMID: 27554821Free PMC Article
Sethuraman G, Marwaha RK, Challa A, Yenamandra VK, Ramakrishnan L, Thulkar S, Sharma VK
Pediatrics 2016 Jan;137(1) Epub 2015 Dec 31 doi: 10.1542/peds.2015-1313. PMID: 26721572
Fischer J, Faure A, Bouadjar B, Blanchet-Bardon C, Karaduman A, Thomas I, Emre S, Cure S, Ozgüc M, Weissenbach J, Prud'homme JF
Am J Hum Genet 2000 Mar;66(3):904-13. doi: 10.1086/302814. PMID: 10712205Free PMC Article

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