Harlequin Ichthyosis

Harlequin ichthyosis is the most severe form of autosomal recessive congenital ichthyosis. Newborns have massive plate-like hyperkeratosis with deep fissures, ectropion and eclabium, creating immediate risks of respiratory restriction, dehydration, electrolyte disturbance, infection and impaired feeding. More info

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Genetics

Caused by biallelic loss-of-function variants in ABCA12. Genotypes retaining partial ABCA12 function may produce less severe autosomal recessive congenital ichthyosis phenotypes.

Molecular Mechanism

ABCA12 transports lipids into epidermal lamellar granules. Its loss prevents normal extracellular lipid-layer formation, disrupts desquamation and causes profound failure of the stratum-corneum permeability barrier.

Therapy

Immediate neonatal intensive care requires humidification, fluid and electrolyte management, emollients, eye and airway care, nutrition and prompt treatment of infection. Early systemic retinoids can accelerate shedding of constricting plates. Lifelong skin care is required; no curative therapy exists.

CCP Activity

CCP is developing and phenotyping ABCA12-deficient models, with skin barrier function and survival as principal translational endpoints. The programme combines drug-repurposing studies with design and early validation of a gene-replacement strategy.