Autosomal Recessive Congenital Ichthyosis (ARCI, LI, NCIE)

Inheritance:
 autosomal recessive

Incidence / Frequency:
1:100,000 to 1:200,000 live births in European population. Potentially higher frequency in populations with a tradition of consanguineous marriages.

Clinical features:
Generalized, severe scaling of the skin over the entire body, occurring at birth or in the first four postnatal weeks. In most cases, palmar and plantar involvement occurs, which is, however, not the predominant clinical feature. Scaling shape, hardness, color and size vary considerably between patients and do not provide an indication regarding the underlying genetic defect. Marked differences in the nature of scaling (thickness/color) may also exist between different areas of the patient skin. Some patients show redness of the skin beneath the scaling, which is referred to as erythema. If scaling on the head is very severe, it may impair hair growth. Many patients are unable to sweat or to sweat sufficiently. This causes heat intolerance. Many patients with congenital ichthyosis are born as so-called collodium babies: The newborn is encased in a parchment-like membrane. This membrane bursts within the first days and new, sensitive skin becomes visible. Since the collodion membrane is very thick, complications in terms of closing of the eyelid (ectropion) may occur. Also, the lip may be torn outward due to the thick membrane (eclabium). In most cases, eclabium and ectropion disappear when the collodion membrane dries and peels away. While the collodion membrane is present, no statement regarding the type and severity of ichthyosis is possible. There are cases where, at a later time, no or only minor scaling is visible (self-healing collodium baby [6]).

Genetic cause(s):
Autosomal recessive congenital ichthyosis (ARCI), also called lamellar ichthyosis and non-bullous congenital ichthyosiform erythroderma, are both clinically and genetically very heterogenous. To date, 6 different gene loci have been described for ARCI, while the causative genes are only known for the gene loci on 14q11.2 (TGM1), 17p13.1 (ALOX12B and ALOXE3), 2q34-q35 (ABCA12), 5q33 (ichthyin), and 19p12-q12 ( FLJ39501 ) . Gene locus 19p13.1-13.2 has not yet been described in detail. Mutations in ABCA12 have so far only been identified in patients with an ethnic background from Northern Africa. About 30 % of all affected individuals are carriers of mutations in TGM1, an additional 12 % shows sequence alterations in one of the two genes ALOX12B or ALOXE3. There are no sufficient data available yet to make any statements regarding the frequency of mutations in the ichthyin gene.

Available diagnosis:

Databases and related links:
OMIM: see Table 1
www.RoughSkin.de
NIRK (www.netzwerk-ichthyose.de)
F.I.R.S.T. (www.ScalySkin.org)
Selbsthilfe Ichthyose e.V. (www.ichthyose.de)

Contact / Shipment of samples:
Since autosomal recessive congenital ichthyoses are one of our group’s key research areas, we are very interested in receiving blood and skin specimens from patients and members of their families, in particular if their pedigree indicates consanguinity.

Please call us before collecting and shipping any specimens:

PD Dr. Hans Christian Hennies
University of Cologne
Cologne Center for Genomics
Div. of Dermatogenetics
Zülpicher Str. 47
50674 Cologne
 
E-Mail:
Phone: +49.221.470-6911 or -1350
Fax: +49.221.470-1595

 

Testing is offered under a joint project of Cologne Center for Genomics (Dermatogenetics department) and Institute of Human Genetics, Cologne


At the Institute of Human Genetics, please contact Prof. Dr. Brunhilde Wirth. (See Staff)

 

References:

  1. Krieg P, Marks F, Furstenberger G A gene cluster encoding human epidermis-type lipoxygenases at chromosome 17p13.1: cloning, physical mapping, and expression. Genomics 2001 May 1;73(3):323-30.

  2. Krebsova A, Kuster W, Lestringant G, Schulze B, Hinz B, Frossard PM, Reis A, Hennies HC Identification, by homozygosity mapping, of a novel locus for autosomal recessive congenital ichthyosis on chromosome 17p, and evidence for further genetic heterogeneity. Am. J. Hum. Genet.2001 69: 216-222.

  3. Jobard F, Lefevre C, Karaduman A, Blanchet-Bardon C, Emre S, Weissenbach J, Ozguc M, Lathrop M, Prud’homme JF, Fischer J Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1. Hum. Molec. Genet.2002, 11: 107-113.

  4. Yu Z, Schneider C, Boeglin WE, Brash AR Mutations associated with a congenital form of ichthyosis (NCIE) inactivate the epidermal lipoxygenases 12R-LOX and eLOX3. Biochim Biophys Acta. 2005 Jan 5;1686 3:238-47.

  5. Lefevre C, Bouadjar B, Karaduman A, Jobard F, Saker S, Ozguc M, Lathrop M, Prud’homme JF, Fischer J Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis. Hum Mol Genet. 2004 Oct 15;13(20):2473-82.

  6. Raghunath M, Hennies HC, Ahvazi B, Vogel M, Reis A, Steinert PM, Traupe H Self-healing collodion baby: a dynamic phenotype explained by a particular transglutaminase-1 mutation. J. Invest. Derm.2003, 120: 224-228.

  7. Huber M, Rettler I, Bernasconi K, Frenk E, Lavrijsen SPM, Ponec M, Bon A, Lautenschlager S, Schorderet DF, Hohl D Mutations of keratinocyte transglutaminase in lamellar ichthyosis. Science 1995, 267: 525-528.

  8. Hennies HC, Kuster W, Wiebe V, Krebsova A, Reis A Genotype/phenotype correlation in autosomal recessive lamellar ichthyosis. Am J Hum Genet. 1998 May;62(5):1052-61.

  9. Katja-Martina Eckl, Peter Krieg, Wolfgang Küster, Heiko Traupe, Françoise André, Nadine Wittstruck, Gerhard Fürstenberger, Hans Christian Hennies Mutation spectrum and functional analysis of epidermis-type lipoxygenases in patients with autosomal recessive congenital ichthyosis. Hum Mutat. 2005 Aug 22;26(4):351-361.

 

 

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