What is Harlequin Ichhyosis?

A severe inherited skin condition called harlequin ichthyosis affects the skin. The majority of the bodies of newborns with this syndrome are covered in extremely thick, rigid skin. Deep fractures divide the huge, diamond-shaped plates that the skin develops (fissures). These skin flaws restrict arm and leg movement and change the appearance of the eyes, nose, mouth, and ears. Babies with harlequin ichthyosis may experience breathing problems and respiratory failure due to restricted chest mobility. Infants with the condition also have eating issues.

Normally, the skin creates a barrier of protection between the body and its surroundings. Harlequin ichthyosis-related skin defects compromise this barrier, making it challenging for afflicted newborns to balance water loss, maintain a stable body temperature, and fight infections. In the first few weeks of life, infants with harlequin ichthyosis frequently undergo excessive fluid loss (dehydration) and acquire infections that can be fatal.

After the neonatal stage, the thick skin plates are removed, and the skin becomes reddened and covered with scales.

The survival of afflicted infants during the neonatal period was quite uncommon. Because of rigorous medical care and improved therapy, babies with this condition now have a higher chance of surviving into infancy and early adulthood.

Also known as Autosomal recessive congenital ichthyosis 4B, this disorder is inherited.

Numerous nonsyndromic ichthyoses fall under autosomal recessive congenital ichthyosis (ARCI). Although collodion infants make up most ARCI cases, the clinical appearance and severity of ARCI can vary greatly. For example, lamellar ichthyosis (LI), (nonbullous) congenital ichthyosiform erythroderma, and harlequin ichthyosis are some of the more severe and frequently deadly forms (CIE). Although it is now known that these characteristics exist on a continuum, phenotypic descriptions are still helpful in the clinical setting for elucidating prognosis and treatment. The thick, rigid, armor-like plates of cornified skin covering preterm infants with harlequin ichthyosis severely limit mobility. Respiratory distress, feeding issues, and systemic infection are all life-threatening postpartum complications. Collodion newborns are born with a whole body covered in a tight, glossy, transparent, or opaque membrane that lasts for days to weeks. LI and CIE’s phenotypes appear to differ: typical, severe LI has a dark brown, plate-like scale without erythroderma, whereas CIE has a thinner, whiter scale with underlying widespread skin redness. Ectropion, eclabium, scarring alopecia affecting the scalp and eyebrows, and palmar and plantar keratoderma are all symptoms of severe involvement. A few uncommon nonsyndromic ichthyoses, including bathing suit ichthyosis, self-improving collodion ichthyosis, and ichthyosis-prematurity syndrome, have also been identified.

Frequency

The exact incidence of harlequin ichthyosis is unclear. However, it is highly unusual.

Causes

Variations bring Harlequin ichthyosis, usually referred to as mutations, in the ABCA12 gene. Instructions for creating a protein that is necessary for the typical growth of skin cells are provided by the ABCA12 gene. This protein is essential for transporting lipids and enzymes in the epidermis (the epidermis).

Certain ABCA12 gene variations stop cells from producing any ABCA12 protein. Other variations result in the synthesis of an unusually tiny protein that is incapable of properly transporting lipids. The normal growth of the epidermis before and after birth is hampered by a lack of functional ABCA12 protein, which causes severe skin defects that are distinctive of harlequin ichthyosis.

Inheritance

Due to variations in both copies of the gene in each cell, this disorder is inherited in an autosomal recessive manner. A person with an autosomal recessive disorder has one copy of the mutated gene in each parent, but usually, neither parent exhibits the disease’s symptoms.

Diagnosis/testing.

Skin conditions present at birth and during early childhood are used to diagnose nonsyndromic ARCI. The diagnosis of ARCI can be made without a skin biopsy. At least 15% of afflicted families do not contain pathogenic mutations in any of the twelve genes known to be related to ARCI: ABCA12, ALOX12B, ALOXE3, CASP14, CERS3, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, and TGM1. The ideal diagnostic test is a multigene panel that contains these genes. Suppose this type of testing is not accessible. In that case, single-gene testing should be considered, starting with ABCA12 in those with harlequin ichthyosis, TGM1 in those with ARCI without a harlequin appearance at birth, and SLC27A4 in those with the ichthyosis-prematurity syndrome.

Management and Treatment 

To treat manifestations, neonates should be kept in a moist environment in an isolette, infections should be treated hygienically, and petrolatum-based creams and ointments should be used to keep the skin soft, supple, and hydrated. For older children, humidification with long baths, lubrication, and keratolytic agents such as alpha-hydroxy acid or urea preparations should be used to promote peeling and thinning.

Secondary complications’ avoidance: High-calorie meal; when necessary, the release of collodion membrane on fingers to maintain circulation and on the thorax for proper breathing. Prevention of infection, dehydration and, hyperthermia, ocular dryness.

Monitoring: Consistent physical examination to check for signs of infection, treat skin involvement, and check for the elevated (but still low) risk of skin cancer (squamous cell carcinoma, basal cell carcinoma, atypical melanocytic nevi, or malignant melanoma).

Agents or situations to avoid: Overheating and skin irritation.

Genetic guidance.

Autosomal recessive inheritance is how ARCI is transmitted. Each affected person’s sibling has a 25% risk of developing the disease, a 50% chance of becoming an asymptomatic carrier, and a 25% chance of remaining unaffected and not a carrier. If both ARCI-related pathogenic variants have been found in a family, carrier testing for at-risk relatives and prenatal testing for a fetus at elevated risk are both options.

References

https://medlineplus.gov/genetics/condition/harlequin-ichthyosis

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