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Autosomal recessive congenital ichthyosis 2(ARCI2)

MedGen UID:
854762
Concept ID:
C3888093
Disease or Syndrome
Synonym: ARCI2
 
Genes (locations): ALOX12B (17p13.1); ALOXE3 (17p13.1)
 
Monarch Initiative: MONDO:0009439
OMIM®: 242100

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 discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300).  http://www.omim.org/entry/242100
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
External genital hypoplasia
MedGen UID:
344478
Concept ID:
C1855333
Finding
Underdevelopment of part or all of the external reproductive organs.
Short toe
MedGen UID:
322858
Concept ID:
C1836195
Finding
A toe that appears disproportionately short compared to the foot.
Short finger
MedGen UID:
334977
Concept ID:
C1844548
Anatomical Abnormality
Abnormally short finger associated with developmental hypoplasia.
Palmar hyperlinearity
MedGen UID:
400466
Concept ID:
C1864168
Finding
Exaggerated skin markings (dermatoglyphics) on the palms of the hand.
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.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Intellectual disability, borderline
MedGen UID:
507499
Concept ID:
C0006009
Finding
Borderline intellectual disability is defined as an intelligence quotient (IQ) in the range of 70-85.
Paralysis
MedGen UID:
105510
Concept ID:
C0522224
Finding
Paralysis of voluntary muscles means loss of contraction due to interruption of one or more motor pathways from the brain to the muscle fibers. Although the word paralysis is often used interchangeably to mean either complete or partial loss of muscle strength, it is preferable to use paralysis or plegia for complete or severe loss of muscle strength, and paresis for partial or slight loss. Motor paralysis results from deficits of the upper motor neurons (corticospinal, corticobulbar, or subcorticospinal). Motor paralysis is often accompanied by an impairment in the facility of movement.
Ectropion
MedGen UID:
4448
Concept ID:
C0013592
Disease or Syndrome
An outward turning (eversion) or rotation of the eyelid margin.
Everted lower lip vermilion
MedGen UID:
344003
Concept ID:
C1853246
Finding
An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
Anhidrosis
MedGen UID:
1550
Concept ID:
C0003028
Disease or Syndrome
Inability to sweat.
Hypohidrosis
MedGen UID:
43796
Concept ID:
C0020620
Disease or Syndrome
Abnormally diminished capacity to sweat.
Erythema
MedGen UID:
11999
Concept ID:
C0041834
Disease or Syndrome
Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.
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.
Congenital ichthyosiform erythroderma
MedGen UID:
86936
Concept ID:
C0079583
Disease or Syndrome
An ichthyosiform abnormality of the skin with congenital onset.
Abnormal hair morphology
MedGen UID:
56381
Concept ID:
C0157733
Finding
An abnormality of the hair.
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).
Small nail
MedGen UID:
537942
Concept ID:
C0263523
Finding
A nail that is diminished in length and width, i.e., underdeveloped nail.
Thin nail
MedGen UID:
98073
Concept ID:
C0423823
Finding
Nail that appears thin when viewed on end.
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.
Hypergranulosis
MedGen UID:
481177
Concept ID:
C3279547
Finding
Hypergranulosis is an increased thickness of the stratum granulosum.

Professional guidelines

PubMed

Ennouri M, Zimmer AD, Bahloul E, Chaabouni R, Marrakchi S, Turki H, Fakhfakh F, Bougacha-Elleuch N, Fischer J
BMC Med Genomics 2022 Jan 5;15(1):4. doi: 10.1186/s12920-021-01154-z. PMID: 34983512Free PMC Article
Simpson JK, Martinez-Queipo M, Onoufriadis A, Tso S, Glass E, Liu L, Higashino T, Scott W, Tierney C, Simpson MA, Desomchoke R, Youssefian L, SaeIdian AH, Vahidnezhad H, Bisquera A, Ravenscroft J, Moss C, O'Toole EA, Burrows N, Leech S, Jones EA, Lim D, Ilchyshyn A, Goldstraw N, Cork MJ, Darne S, Uitto J, Martinez AE, Mellerio JE, McGrath JA
Br J Dermatol 2020 Mar;182(3):729-737. Epub 2019 Aug 26 doi: 10.1111/bjd.18211. PMID: 31168818
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849

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
Ennouri M, Zimmer AD, Bahloul E, Chaabouni R, Marrakchi S, Turki H, Fakhfakh F, Bougacha-Elleuch N, Fischer J
BMC Med Genomics 2022 Jan 5;15(1):4. doi: 10.1186/s12920-021-01154-z. PMID: 34983512Free PMC Article
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
Traupe H, Fischer J, Oji V
J Dtsch Dermatol Ges 2014 Feb;12(2):109-21. Epub 2013 Oct 11 doi: 10.1111/ddg.12229. PMID: 24119255
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849

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
Londhe MM, Patil TV, Suryawanshi KH
Indian J Pathol Microbiol 2022 Apr-Jun;65(2):462-464. doi: 10.4103/IJPM.IJPM_1150_20. PMID: 35435396
Traupe H, Fischer J, Oji V
J Dtsch Dermatol Ges 2014 Feb;12(2):109-21. Epub 2013 Oct 11 doi: 10.1111/ddg.12229. PMID: 24119255
Akiyama M
J Dermatol Sci 2006 May;42(2):83-9. Epub 2006 Feb 14 doi: 10.1016/j.jdermsci.2006.01.003. PMID: 16481150
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849

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
Murase Y, Takeichi T, Kawamoto A, Tanahashi K, Okuno Y, Takama H, Shimizu E, Ishikawa J, Ogi T, Akiyama M
J Dermatol Sci 2020 Jan;97(1):50-56. Epub 2019 Dec 4 doi: 10.1016/j.jdermsci.2019.12.001. PMID: 31836270
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
Oji V, Tadini G, Akiyama M, Blanchet Bardon C, Bodemer C, Bourrat E, Coudiere P, DiGiovanna JJ, Elias P, Fischer J, Fleckman P, Gina M, Harper J, Hashimoto T, Hausser I, Hennies HC, Hohl D, Hovnanian A, Ishida-Yamamoto A, Jacyk WK, Leachman S, Leigh I, Mazereeuw-Hautier J, Milstone L, Morice-Picard F, Paller AS, Richard G, Schmuth M, Shimizu H, Sprecher E, Van Steensel M, Taïeb A, Toro JR, Vabres P, Vahlquist A, Williams M, Traupe H
J Am Acad Dermatol 2010 Oct;63(4):607-41. doi: 10.1016/j.jaad.2009.11.020. PMID: 20643494
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849

Prognosis

Charfeddine C, Laroussi N, Mkaouar R, Jouini R, Khayat O, Redissi A, Mosbah A, Dallali H, Chedly Debbiche A, Zaouak A, Fenniche S, Abdelhak S, Hammami-Ghorbel H
PLoS One 2021;16(10):e0258777. Epub 2021 Oct 20 doi: 10.1371/journal.pone.0258777. PMID: 34669720Free PMC Article
Li L, Liu W, Xu Y, Li M, Tang Q, Yu B, Cai R, Liu S
Mol Genet Genomic Med 2020 Feb;8(2):e1076. Epub 2019 Dec 13 doi: 10.1002/mgg3.1076. PMID: 31833240Free PMC Article
Simpson JK, Martinez-Queipo M, Onoufriadis A, Tso S, Glass E, Liu L, Higashino T, Scott W, Tierney C, Simpson MA, Desomchoke R, Youssefian L, SaeIdian AH, Vahidnezhad H, Bisquera A, Ravenscroft J, Moss C, O'Toole EA, Burrows N, Leech S, Jones EA, Lim D, Ilchyshyn A, Goldstraw N, Cork MJ, Darne S, Uitto J, Martinez AE, Mellerio JE, McGrath JA
Br J Dermatol 2020 Mar;182(3):729-737. Epub 2019 Aug 26 doi: 10.1111/bjd.18211. PMID: 31168818
Oji V, Tadini G, Akiyama M, Blanchet Bardon C, Bodemer C, Bourrat E, Coudiere P, DiGiovanna JJ, Elias P, Fischer J, Fleckman P, Gina M, Harper J, Hashimoto T, Hausser I, Hennies HC, Hohl D, Hovnanian A, Ishida-Yamamoto A, Jacyk WK, Leachman S, Leigh I, Mazereeuw-Hautier J, Milstone L, Morice-Picard F, Paller AS, Richard G, Schmuth M, Shimizu H, Sprecher E, Van Steensel M, Taïeb A, Toro JR, Vabres P, Vahlquist A, Williams M, Traupe H
J Am Acad Dermatol 2010 Oct;63(4):607-41. doi: 10.1016/j.jaad.2009.11.020. PMID: 20643494
DiGiovanna JJ, Robinson-Bostom L
Am J Clin Dermatol 2003;4(2):81-95. doi: 10.2165/00128071-200304020-00002. PMID: 12553849

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
Winter-Paquette LM, Al Suwaidi HH, Sajjad Y, Bricker L
Eur J Med Genet 2022 May;65(5):104501. Epub 2022 Apr 1 doi: 10.1016/j.ejmg.2022.104501. PMID: 35378319
Charfeddine C, Laroussi N, Mkaouar R, Jouini R, Khayat O, Redissi A, Mosbah A, Dallali H, Chedly Debbiche A, Zaouak A, Fenniche S, Abdelhak S, Hammami-Ghorbel H
PLoS One 2021;16(10):e0258777. Epub 2021 Oct 20 doi: 10.1371/journal.pone.0258777. PMID: 34669720Free PMC Article
Li L, Liu W, Xu Y, Li M, Tang Q, Yu B, Cai R, Liu S
Mol Genet Genomic Med 2020 Feb;8(2):e1076. Epub 2019 Dec 13 doi: 10.1002/mgg3.1076. PMID: 31833240Free PMC Article
Simpson JK, Martinez-Queipo M, Onoufriadis A, Tso S, Glass E, Liu L, Higashino T, Scott W, Tierney C, Simpson MA, Desomchoke R, Youssefian L, SaeIdian AH, Vahidnezhad H, Bisquera A, Ravenscroft J, Moss C, O'Toole EA, Burrows N, Leech S, Jones EA, Lim D, Ilchyshyn A, Goldstraw N, Cork MJ, Darne S, Uitto J, Martinez AE, Mellerio JE, McGrath JA
Br J Dermatol 2020 Mar;182(3):729-737. Epub 2019 Aug 26 doi: 10.1111/bjd.18211. PMID: 31168818

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