Autosomal Recessive Congenital Ichthyosis

Autosomal recessive congenital ichthyoses (ARCI) form a heterogeneous group of disorders characterized by generalized scaling and variable degree of redness of the skin. ARCI manifests at birth or infancy, generally without primary involvement of other organ systems (non-syndromic). The skin features of ARCI may overlap considerably with various types of syndromic ichthyoses (see our website www.genedx.com for information on other types of ichthyoses). The 3 major types of non-syndromic ichthyoses include Harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). Most neonates with ARCI present as collodion babies with a taut, translucent or opaque membrane that encases the entire body and lasts for days to two weeks. In severe cases, ectropion, eclabium, and scarring alopecia of the scalp and eyebrows may be present. After shedding the collodion membrane, the presentation and severity of ARCI between individuals can vary significantly. At one end of the spectrum is severe ‘classic’ lamellar ichthyosis (LI), which is characterized by large, dark brown, plate-like scale without underlying erythroderma. At the other end is severe ‘classic’ CIE, with fine, whitish scale and intense redness (erythroderma) of the skin. The clinical features of CIE can be milder than in LI and demonstrate a greater variability in the intensity of redness, scale, and involvement of palms and soles. However, CIE may cause substantial metabolic stress in young children and growth delay. There are also cases of (almost) complete resolution of the skin disorder, so-called ‘self-healing collodion ichthyosis’. Distinguishing between these disorders on clinical grounds can be useful for clarifying prognosis and management and, to some extent, to choose which genes to analyze. A skin biopsy is not necessary to establish the diagnosis of ARCI, and is usually not helpful in differentiating among the different clinical disorders along the spectrum. However, a skin biopsy is useful to differentiate ARCI from the bullous forms of ichthyosis (epidermolytic ichthyosis, also known as epidermolytic hyperkeratosis).

Tests Available

Forms and Documents

Test Details

ALOX12B
  • Confirmation of the clinical diagnosis in any child born with a collodion membrane in whom a TGM1 mutation has been ruled out
  • Confirmation of the clinical diagnosis in any individual with non-bullous congenital ichthyosiform erythroderma
  • Identification of at-risk family members
  • Prenatal diagnosis
  • Capillary Sequencing Reflex to Exon Array

Ordering

1151
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 757.1 Ichthyosis congenita, Congenital ichthyosis, Harlequin fetus, Ichthyosiform erythroderma
  • 757.39 Other Accessory skin tags, congenital, Congenital scar, Epidermolysis bullosa, Keratoderma (congenital)
* For price inquiries please email zebras@genedx.com

References

  1. Lobard et al. Lipoxygenase-3 (ALOXE3) and 12B-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1. Hum Mol Genet 11:107-113, 2002.
  2. Eckl et al. Mutation spectrum and functional analysis of epidermis-type lioxygenases in patients with autosomal recessive congenital ichthyosis. Hum Mutat. 2005 Oct;26(4):351-61.
  3. Dahlqvist et al., Congenital ichthyosis: Mutations in ichthyin associated with specific structural abnormalities in the granular layer of epidermis. J Med Genet 44: 615-620, 2007.
  4. Lefevre et al. Mutations in ichthyin a new gene on chromosome 5q33, in a new form of autosomal recessive congenital ichthyosis. Hum Mol Genet 13:2473-2482, 2004.

Forms and Documents

Test Details

ALOXE3
  • Confirmation of the clinical diagnosis in any child born with a collodion membrane in whom a TGM1 mutation has been ruled out
  • Confirmation of the clinical diagnosis in any individual with non-bullous congenital ichthyosiform erythroderma
  • Identification of at-risk family members
  • Prenatal diagnosis
  • Capillary Sequencing Reflex to Exon Array

Ordering

1152
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 757.1 Ichthyosis congenita, Congenital ichthyosis, Harlequin fetus, Ichthyosiform erythroderma
  • 757.39 Other Accessory skin tags, congenital, Congenital scar, Epidermolysis bullosa, Keratoderma (congenital)
* For price inquiries please email zebras@genedx.com

References

  1. Lobard et al. Lipoxygenase-3 (ALOXE3) and 12B-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1. Hum Mol Genet 11:107-113, 2002.
  2. Dahlqvist et al., Congenital ichthyosis: Mutations in ichthyin associated with specific structural abnormalities in the granular layer of epidermis. J Med Genet 44: 615-620, 2007.
  3. Lefevre et al. Mutations in ichthyin a new gene on chromosome 5q33, in a new form of autosomal recessive congenital ichthyosis. Hum Mol Genet 13:2473-2482, 2004.
  4. Eckl et al. Mutation spectrum and functional analysis of epidermis-type lioxygenases in patients with autosomal recessive congenital ichthyosis. Hum Mutat. 2005 Oct;26(4):351-61.

Forms and Documents

Test Details

CYP4F22
  • Confirmation of the clinical diagnosis and differentiating between the various forms of congenital ichthyosis
  • Identification of at-risk family members
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

637
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
No
Yes
  • 757.1 Ichthyosis congenita, Congenital ichthyosis, Harlequin fetus, Ichthyosiform erythroderma
  • 757.39 Other Accessory skin tags, congenital, Congenital scar, Epidermolysis bullosa, Keratoderma (congenital)
* For price inquiries please email zebras@genedx.com

References

  1. Herman M. et al. (2009) Transglutaminase-1 gene mutations in autosomal recessive congenital ichthyosis: summary of mutations (including 23 novel) and modeling of TGase-1. Hum Mutat. 30:537-47.
  2. Eckl K. et al. (2009) Molecular Analysis of 250 Patients with Autosomal Recessive Congenital Ichthyosis: Evidence for Mutation Hotspots in ALOXE3 and Allelic Heterogeneity in ALOX12B. J Invest Derm. 129: 1421-1428.
  3. Fischer J. et al. (2009) Autosomal Recessive Congenital Ichthyosis. J Invest Derm. 129:1319-1321.
  4. Eckl K. et al. (2005) Mutation spectrum and functional analysis of epidermis-type lioxygenases in patients with autosomal recessive congenital ichthyosis. Hum Mut. 26:351-61. (3) Lefevre C. et al. (2004) Mutations in ichthyin a new gene on chromosome 5q3
  5. Jobard F. et al. (2002) Lipoxygenase-3 (ALOXE3) and 12B-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1. Hum Mol Genet 11:107-11.
  6. Lefevre C. et al. (2004) Mutations in ichthyin a new gene on chromosome 5q33, in a new form of autosomal recessive congenital ichthyosis. Hum Mol Genet 13:2473-2482.
  7. Dahlqvist J. et al. (2007) Congenital ichthyosis: Mutations in ichthyin associated with specific structural abnormalities in the granular layer of epidermis. J Med Genet 44: 615- 620.
  8. Lefevre C. et al. (2006) Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. Hum Mol Genet. 15:767-776.

Forms and Documents

Test Details

NIPAL4(Ichthyin)
  • Confirmation of the clinical diagnosis in any child born with a collodion membrane in whom a TGM1 mutation has been ruled out
  • Confirmation of the clinical diagnosis in any individual with non-bullous congenital ichthyosiform erythroderma
  • Identification of at-risk family members
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

1153
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
No
Yes
  • 757.1 Ichthyosis congenita, Congenital ichthyosis, Harlequin fetus, Ichthyosiform erythroderma
  • 757.39 Other Accessory skin tags, congenital, Congenital scar, Epidermolysis bullosa, Keratoderma (congenital)
* For price inquiries please email zebras@genedx.com

References

  1. Lobard et al. Lipoxygenase-3 (ALOXE3) and 12B-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1. Hum Mol Genet 11:107-113, 2002
  2. Eckl et al. Mutation spectrum and functional analysis of epidermis-type lioxygenases in patients with autosomal recessive congenital ichthyosis. Hum Mutat. 2005 Oct;26(4):351-61
  3. Lefevre et al. Mutations in ichthyin a new gene on chromosome 5q33, in a new form of autosomal recessive congenital ichthyosis. Hum Mol Genet 13:2473-2482, 2004
  4. Dahlqvist et al., Congenital ichthyosis: Mutations in ichthyin associated with specific structural abnormalities in the granular layer of epidermis. J Med Genet 44: 615-620, 2007

Forms and Documents

Test Details

TGM1
  • Confirmation of a clinical diagnosis
  • Carrier testing in unaffected family members
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

125
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
Yes
Yes
  • 757.1 Ichthyosis congenita, Congenital ichthyosis, Harlequin fetus, Ichthyosiform erythroderma
  • 757.39 Other Accessory skin tags, congenital, Congenital scar, Epidermolysis bullosa, Keratoderma (congenital)
* For price inquiries please email zebras@genedx.com

References

  1. Huber M, et al., Mutations of keratinocyte transglutaminase in lamellar ichthyosis. Science 267:525-8 (1995)
  2. Russell LJ, et al., Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis. Nat Genet 9:279-83 (1995)
  3. Shevchenko YO, et al., Splice-site mutation in TGM1 in congenital recessive ichthyosis in American families: molecular, genetic, genealogic, and clinical studies. Hum Genet 106:492-9 (2000).

Forms and Documents

Test Details

ABCA12, ABHD5, AGPS, ALDH3A2, ALOX12B, ALOXE3, AP1S1, ARSE, CASP14, CERS3, CLDN1, CYP4F22, EBP, ELOVL4, FLG, GJB2 (Cx26), GJB3 (Cx31), GJB4 (Cx30.3), GJB6 (Cx30), KRT1, KRT10, KRT2, KRT9, LIPN, LOR, NIPAL4(Ichthyin), PEX7, PHGDH, PHYH, PNPLA1, PNPLA2, POMP, PSAT1, SDR9C7, SLC27A4, SNAP29, SPINK5, ST14, STS, TGM1, TGM5, VPS33B, ZMPSTE24
  • Identification of the specific molecular basis of congential ichthyosis or related skin disorders
  • Genetic counseling and recurrence risk assessment
  • Option for prenatal testing in future pregnancies

As needed, based on the referring diagnosis and coverage achieved by the XomeDxSlice-Ichthyosis for a given patient, critical exons with a high yield of mutations will be filled-in by dideoxy sequencing. For any autosomal recessive gene, if one definitive mutation is found by XomeDxSlice sequencing, AND the gene fits the type of ichthyosis reported by the referring physician, capillary sequencing will be used to fill in sequence for exons that are not sufficiently covered (>10X) to find the second mutation. If no second mutation is found by sequencing, deletion/duplication analysis of that gene can be performed at no additional cost can be performed at no additional cost.

Patient samples sent for XomeDxSlice will not be evaluated for secondary findings and therefore will not receive secondary findings as part of their result.\\\"

  • Next-Gen Sequencing

Ordering

708
6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81252x1, 81254x1, 81479x11
Yes
Yes
* For price inquiries please email zebras@genedx.com