Nonbullous congenital ichthyosiform erythroderma

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.

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.

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

NBCIE is estimated to affect 1 in 200,000 to 300,000 individuals in the United States. This condition is more common in Norway, where an estimated 1 in 90,000 people are affected.

Mutations in several genes can cause NBCIE. Mutations in the ABCA12, ALOX12B, or ALOXE3 gene are responsible for most of cases of NBCIE. Mutations in other genes are each found in only a small percentage of cases. All of the genes associated with NBCIE provide instructions for making proteins that are found in the outermost layer of the skin (the epidermis). The epidermis forms a protective barrier between the body and its surrounding environment. Gene mutations impair the respective protein's function or structure within the epidermis, which prevents this outermost layer of skin from being an effective barrier before and after birth. The abnormal skin cannot protect against fluid loss (dehydration) or the outside environment, leading to problems controlling body temperature; dry skin; the formation of fine, white scales; and increased risk of infections in people with NBCIE. The skin scales can impair the function of sweat glands under the skin, causing anhidrosis.

In some people with NBCIE, the cause of the disorder is unknown. Researchers are looking for additional genes that are associated with NBCIE.

Genetic Testing Information

• Genetic Testing Registry: Autosomal recessive congenital ichthyosis 10
• Genetic Testing Registry: Autosomal recessive congenital ichthyosis 2
• Genetic Testing Registry: Autosomal recessive congenital ichthyosis 3
• Genetic Testing Registry: Autosomal recessive congenital ichthyosis 4A
• Genetic Testing Registry: Autosomal recessive congenital ichthyosis 5
• Genetic Testing Registry: Autosomal recessive congenital ichthyosis 6
• Genetic Testing Registry: Autosomal recessive congenital ichthyosis 9
• Genetic Testing Registry: Ichthyosis, congenital, autosomal recessive 12

Genetic and Rare Diseases Information Center

• Congenital non-bullous ichthyosiform erythroderma

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 4A; ARCI4A
• ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 2; ARCI2
• ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 5; ARCI5
• ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 3; ARCI3
• ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 6; ARCI6
• ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 12; ARCI12
• ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 9; ARCI9
• ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 10; ARCI10

Scientific Articles on PubMed

• PubMed

• Boyden LM, Craiglow BG, Hu RH, Zhou J, Browning J, Eichenfield L, Lim YL, Luu M, Randolph LM, Ginarte M, Fachal L, Rodriguez-Pazos L, Vega A, Kramer D, Yosipovitch G, Vahidnezhad H, Youssefian L, Uitto J, Lifton RP, Paller AS, Milstone LM, Choate KA. Phenotypic spectrum of autosomal recessive congenital ichthyosis due to PNPLA1 mutation. Br J Dermatol. 2017 Jul;177(1):319-322. doi: 10.1111/bjd.15570. Epub 2017 Jun 7. No abstract available. Citation on PubMed
• Eckl KM, de Juanes S, Kurtenbach J, Natebus M, Lugassy J, Oji V, Traupe H, Preil ML, Martinez F, Smolle J, Harel A, Krieg P, Sprecher E, Hennies HC. Molecular analysis of 250 patients with autosomal recessive congenital ichthyosis: evidence for mutation hotspots in ALOXE3 and allelic heterogeneity in ALOX12B. J Invest Dermatol. 2009 Jun;129(6):1421-8. doi: 10.1038/jid.2008.409. Epub 2009 Jan 8. Citation on PubMed
• Eckl KM, Krieg P, Kuster W, Traupe H, Andre F, Wittstruck N, Furstenberger G, Hennies HC. Mutation spectrum and functional analysis of epidermis-type lipoxygenases in patients with autosomal recessive congenital ichthyosis. Hum Mutat. 2005 Oct;26(4):351-61. doi: 10.1002/humu.20236. Citation on PubMed
• Kirchmeier P, Zimmer A, Bouadjar B, Rosler B, Fischer J. Whole-Exome-Sequencing Reveals Small Deletions in CASP14 in Patients with Autosomal Recessive Inherited Ichthyosis. Acta Derm Venereol. 2017 Jan 4;97(1):102-104. doi: 10.2340/00015555-2510. No abstract available. Citation on PubMed
• Krieg P, Furstenberger G. The role of lipoxygenases in epidermis. Biochim Biophys Acta. 2014 Mar;1841(3):390-400. doi: 10.1016/j.bbalip.2013.08.005. Epub 2013 Aug 16. Erratum In: Biochim Biophys Acta. 2014 Dec;1841(12):1767. Citation on PubMed
• Nawaz S, Tariq M, Ahmad I, Malik NA, Baig SM, Dahl N, Klar J. Non-bullous congentital ichthyosiform erythroderma associated with homozygosity for a novel missense mutation in an ATP binding domain of ABCA12. Eur J Dermatol. 2012 Mar-Apr;22(2):178-81. doi: 10.1684/ejd.2011.1638. Citation on PubMed
• Pigg MH, Bygum A, Ganemo A, Virtanen M, Brandrup F, Zimmer AD, Hotz A, Vahlquist A, Fischer J. Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia: Clinical Characteristics and Novel and Recurrent Mutations in 132 Patients. Acta Derm Venereol. 2016 Nov 2;96(7):932-937. doi: 10.2340/00015555-2418. Citation on PubMed
• Takeichi T, Akiyama M. Inherited ichthyosis: Non-syndromic forms. J Dermatol. 2016 Mar;43(3):242-51. doi: 10.1111/1346-8138.13243. Citation on PubMed