autosomal recessive congenital ichthyosis 13

Autosomal Recessive Congenital Ichthyosis 13 (ARCI13) is a rare genetic disorder that affects the skin's ability to produce and shed skin cells properly. This condition is characterized by:

• Abnormal skin scaling: The skin presents with lamellar ichthyosis, which means it has thick, plate-like scales that cover the body.
• Ectropion and eclabium: The eyelids (ectropion) and ears (eclabium) may be affected, leading to visible folds or creases in these areas.
• Palmoplantar keratoderma: The palms of the hands and soles of the feet are often severely thickened, with painful fissures and digital contractures.

ARCI13 is caused by a homozygous mutation in the SDR9C7 gene on chromosome 12q13. This genetic defect affects the skin's keratinization process, leading to the characteristic symptoms of this condition.

References:

• [6] states that ARCI13 is characterized by lamellar ichthyosis, ectropion, and palmoplantar keratoderma.
• [7] defines ARCI13 as an autosomal recessive congenital ichthyosis with lamellar ichthyosis, ectropion, and other symptoms.
• [5] mentions that ARCI refers to a group of rare disorders of keratinization, which includes ARCI13.

Autosomal Recessive Congenital Ichthyosis (ARCI) is a rare genetic disorder characterized by abnormal skin scaling. The signs and symptoms of ARCI can vary in severity, but they often include:

• Generalized scaling: A widespread appearance of dry, scaly skin on the body, which can be accompanied by erythroderma (redness of the skin)
• Taut, dark, and split skin: Newborns with ARCI may have skin that is tight, dark, and cracked
• Palmoplantar keratoderma: Thickening of the skin on the palms of the hands and soles of the feet, often accompanied by painful fissures and digital contractures
• Ectropion and eclabium: Drooping eyelids and lips, respectively
• Sparse hair: People with ARCI may have sparse hair, but its structure is normal

These symptoms can be present at birth or appear shortly after. In some cases, the condition may not become apparent until later in life.

References:

• [3] describes HI or harlequin fetus as a severe and usually fatal form of ichthyosis, with children being premature and having extensive shiny hyperkeratotic plaques.
• [5] states that ARCI is characterized primarily by abnormal skin scaling.
• [7] mentions generalized scaling accompanied by erythroderma without blistering in ARCI.
• [8] describes ARCI as a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling.
• [9] refers to ARCI as a group of rare disorders of keratinization classified as nonsyndromic forms of ichthyosis.

Based on the provided context, diagnostic tests for Autosomal Recessive Congenital Ichthyosis (ARCI) include:

• Genetic testing of the blood to determine the presence and type of mutations in the gene responsible for the condition [6].
• Molecular genetics tests such as deletion/duplication analysis and sequence analysis of the ABCA12 gene, which is commonly associated with ARCI [2].

It's worth noting that genetic testing can help pinpoint the specific subtype of ichthyosis a person has, or confirm the diagnosis of ARCI [5]. However, treatment monitoring should also include laboratory work-up with liver function test and lipid profile before starting treatment, then at 1 month and every 3 months thereafter [7][9].

Additionally, exome-based NextGen sequencing with CNV analysis is considered a cost-effective approach for reflexing to PGxome or other exome-based testing approaches [11].

Treatment Options for Autosomal Recessive Congenital Ichthyosis

Autosomal recessive congenital ichthyosis (ARCI) is a rare skin disorder that affects the cornification process, leading to dry, scaly skin. While there is no cure for ARCI, various treatment options are available to manage its symptoms.

Topical Treatments

• Emollients: Daily applications of emollients can help moisturize and soften the skin.
• Keratolytics: These agents can be used to remove dead skin cells, but may not be tolerated by all patients.
• Oral retinoids and vitamin A analogues: These medications can be effective in treating ARCI, but their use should be carefully considered due to potential side effects.

Alternative Therapies

• N-acetylcysteine (NAC): This compound has shown promise in treating children with lamellar ichthyosis.
• Liarozole: A trial is currently underway to evaluate its efficacy and safety for the treatment of lamellar ichthyosis.

Gene Therapy and Enzyme Replacement Therapy

• Gene therapy: This approach aims to correct the genetic defect responsible for ARCI, offering a potential cure.
• Enzyme replacement therapy: This treatment involves replacing deficient enzymes with functional ones, which can help alleviate symptoms.

Other Considerations

• Repositioning strategies: Researchers are exploring the possibility of repositioning existing drugs or biologics to treat ichthyosis, potentially making treatments more accessible and cost-effective.
• Clinical awareness: Increased awareness among clinicians regarding ARCI, genetic counseling issues, and management is essential for providing optimal care.

References

• [5] The prevalence of ARCI is 1 per 138,000 in the general population and 1 per 61,700 among children under 10 years of age.
• [6] N-acetylcysteine has shown good results in treating children with lamellar ichthyosis.
• [9] A trial is underway to evaluate liarozole's efficacy and safety for treating lamellar ichthyosis.
• [13] Repositioning strategies with existing drugs or biologics could ensure more accessible and possibly lower-cost treatments.

Differential Diagnosis of Autosomal Recessive Congenital Ichthyosis

Autosomal recessive congenital ichthyosis (ARCI) is a rare skin disorder characterized by large scales covering the body without significant erythroderma. To distinguish ARCI from other forms of neonatal erythroderma, a comprehensive evaluation strategy is necessary.

Key Points to Consider:

• Clinical Grounds: The differential diagnosis of congenital ichthyosis can be narrowed based on clinical grounds combined with microscopy, biochemical, and genetic testings.
• Syndromic Forms: To distinguish syndromic forms, neurological, ophthalmological, and ear, nose, and throat workup is helpful; X-rays reveal bone changes (in Conradi–Hünermann–Happle syndrome).
• Other Forms of Ichthyosis: Differential diagnosis includes other forms of neonatal erythroderma, especially syndromic ichthyoses (e.g., Netherton syndrome, KID syndrome), congenital ichthyosiform erythroderma, and self-improving collodion ichthyosis.

References:

• [13] As shown in Figure 5, the differential diagnosis of congenital ichthyosis can be narrowed based on clinical grounds combined with microscopy, biochemical, and genetic testings.
• [9] Differential diagnosis includes other forms of neonatal erythroderma, especially syndromic ichthyoses (e.g., Netherton syndrome, KID syndrome), congenital ichthyosiform erythroderma, and self-improving collodion ichthyosis.

Conclusion:

A thorough evaluation strategy is essential to distinguish autosomal recessive congenital ichthyosis from other forms of neonatal erythroderma. This includes clinical grounds combined with microscopy, biochemical, and genetic testings, as well as consideration of syndromic forms and other forms of ichthyosis.