Harlequin Ichthyosis

Updated: Jun 03, 2016
  • Author: Julie Prendiville, MBBCh; Chief Editor: Dirk M Elston, MD  more...
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Harlequin ichthyosis is the most severe form of autosomal recessive congenital ichthyosis. [1] Harlequin ichthyosis is characterized by a profound thickening of the keratin layer in fetal skin. The affected neonate is born with a massive, horny shell of dense, platelike scale and contraction abnormalities of the eyes, ears, mouth, and appendages, as is shown in the images below.

Harlequin ichthyosis. Courtesy of Dr Bernice Krafc Harlequin ichthyosis. Courtesy of Dr Bernice Krafchik.
Harlequin ichthyosis. Courtesy of Jason K Rivers, Harlequin ichthyosis. Courtesy of Jason K Rivers, MD, FRCPC, and Dr Lawler.

The term harlequin derives from the facial appearance and the triangular and diamond-shaped pattern of hyperkeratosis. The newborn's mouth is pulled wide open, mimicking a clown's smile.

Marked eclabium and ectropion are present secondary to the taut, unyielding skin. The ears may be absent or poorly developed. The arms, feet, and digits have flexion contractures and may be hypoplastic. The skin barrier is severely compromised, leading to excessive water loss, electrolyte abnormalities, temperature dysregulation, and an increased risk of life-threatening infection. The tight, armorlike scale can restrict respiration. Poor feeding and impaired intestinal absorption are common.

This disease primarily affects the skin. Other systems may be significantly compromised by the hyperkeratosis and concomitant deformities. Neonates are often born prematurely.

The underlying genetic abnormality in harlequin ichthyosis is a mutation in the lipid-transporter gene ABCA12 on chromosome 2.

Immunohistocytochemical examination of the skin reveals characteristic abnormalities in the structure of lamellar granules and in the expression of epidermal keratin.

In the past, harlequin ichthyosis was uniformly fatal. Improved survival has been achieved with intense supportive care and systemic retinoid therapy in the neonatal period. Patients who survive manifest a debilitating, persistent ichthyosis similar to severe congenital ichthyosiform erythroderma. [1, 2]

Other Medscape articles on ichthyosis include Hereditary and AcquiredIchthyosis Vulgaris, Lamellar Ichthyosis, X-Linked Ichthyosis, and Ichthyosis (ophthalmology focus).




Approximately 200 cases of harlequin ichthyosis have been reported. [3] The incidence is calculated to be around 1 case in 300,000 births. [3]


No racial predilection is known for harlequin ichthyosis. A higher incidence may be encountered in cultures where parental consanguinity is common. [4]


Sex distribution appears to be equal.



The mortality for harlequin ichthyosis rate is high, with worldwide figures approaching 50%. A review of 45 cases by Rajpopat et al found 25 survivors (56%), ranging in age from 10 months to 25 years. Twenty deaths (44%) occurred from day 1 to day 52 and were as likely to be caused by respiratory failure as fulminant sepsis. [4] A Japanese survey of 16 patients reported survival of 81.3% (13 of 16 patients). [5] Respiratory failure, fulminant sepsis, or a combination of both are the most common causes of death in affected newborns. [4]


Patient Education

Advise parents and caregivers that the baby’s appearance will improve after the neonatal period. Emphasize the need for attention to skin lubrication and for compliance with systemic therapy. Teach them to recognize signs of infection.

Congenital ichthyoses can have devastating medical and social consequences. Parents may wish to communicate with other families who have been similarly affected. Patient organizations (eg, The Foundation for Ichthyosis and Related Skin Types [FIRST]) are available in several countries to provide support to families.