Harlequin Ichthyosis: Overview and Genetic Insights

Description

• Severe Genetic Disorder: Harlequin ichthyosis is a severe genetic disorder affecting the skin.
• Symptoms at Birth:
  • Infants born prematurely with hard, thick skin.
  • Skin forms large, diamond-shaped plates with deep cracks (fissures).
  • Affects shape of eyelids, nose, mouth, ears, and movement of limbs.
  • Chest movement restricted, leading to breathing difficulties and potential respiratory failure.
  • Feeding difficulties.
• Barrier Disruption:
  • Disrupts normal skin barrier functions.
  • Difficulties in controlling water loss, regulating body temperature, fighting infections.
  • High risk of dehydration and life-threatening infections in early life.
• Post-Newborn Development:
  • Hard skin plates shed, skin develops widespread scales and redness.
• Survival:
  • Historically rare for survival past the newborn period.
  • Improved survival into childhood and early adulthood with intensive medical support and better treatments.
• Rarity: Very rare condition with unknown exact incidence.

Genetic Cause

• Gene Involved: Variants in the ABCA12 gene are responsible.
• Function of ABCA12: Provides instructions for a protein crucial for normal skin cell development, particularly in lipid and enzyme transport in the epidermis.
• Impact of Gene Variants:
  • Some variants prevent production of ABCA12 protein.
  • Others produce an abnormal protein incapable of proper lipid transport.
  • Disruption in epidermal development leads to characteristic severe skin abnormalities.

Inheritance Pattern

• Autosomal Recessive:
  • Condition inherited in an autosomal recessive pattern.
  • Both gene copies in a cell have variants.
  • Parents carry one copy of the altered gene but typically do not show symptoms.

Alternative Names

• Autosomal recessive congenital ichthyosis 4B
• Harlequin baby syndrome
• HI
• Ichthyosis congenita, harlequin fetus type

References

• Several studies and articles, including those from Hovnanian A., Kelsell DP, and others, provide insights into the clinical and molecular findings of harlequin ichthyosis.
• Important literature from "GeneReviews" and journals like the "Journal of Clinical Investigation" and the "American Journal of Human Genetics" are available for further reading.