Harlequin ichthyosis

Trinh Nguyen, MD*, Eva Racanska, MD**

* Vietnam.

** Inner Vision Women's Ultrasound, Nashville, Tennessee, USA; Department of Obstetrics and Gynecology, University Hospital Brno, Czech Republic.

Introduction

Harlequin ichthyosis/ Ichthyosis congenita is the most severe and often lethal form of congenital ichthyosis. There is extreme thickening of the keratin layer of the skin. The affected fetus is covered in the thick plates of cornified skin separated by deep cracks or fissures. The tight skin causes facial deformities, microcephaly and also contractures of the extremities. The affected neonates are at risk of respiratory distress due to restricted breathing, sepsis, dehydration, temperature instability, feeding problems which can often lead to the fatal consequences.

Incidence for all types of autosomal recessive congenital ichthyosis is 0.05:10,000. The Harlequin ichthyosis is very rare.

Ultrasound findings

  • Head: cracked skin; open eyes, due to severe eversion of the eyelids (ectropion); wide lips, fixed into the wide grimase (eclabium)
  • Skin: thickened with multiple fissures
  • Extremities: deformation, hypoplasia of the fingers and toes
3D ultrasound helps to make the diagnosis.

Inheritance

Harlequin ichthyosis is an autosomal recessive condition. Heterozygotes (carriers) are asymptomatic. Genetic counseling shoud be offered to the parents who are affected or have an affected child. Disease-causing alleles must be identified before prenatal testing is performed.

Differential diagnosis

  • Sjögren-Larsson syndrome
  • Netherton syndrome
  • Gaucher disease
  • Keratitis-ichthyosis-deafness syndrome
  • Trichothiodystrophy ("sulfur-deficient hair")
  • Chanarin-Dorfman syndrome
  • Conradi-Hünermann syndrome (X-linked dominant chondrodysplasia punctata)
  • Hypohidrotic ectodermal dysplasia
  • Bullous autosomal dominant ichthyoses  
Prognosis Prognosis for such an affected individuals used to be very unfavorable. The quality of life improved with introduction of isotretinoin. Long term survival is still very low.  The oldest surviver lives in United Kingdom and is 26 years old at the moment.

Case report The following images present a case of ichthyosis. A 39-year-old G4P3 with non-contributive personal or family history was referred to our hospital at 29 weeks of gestation due to an anomaly of the face. We performed an ultrasound scan and confirmed the facial anomaly together with multiple other findings:

  • Face with thick lips; cracked skin
  • Skin, thick and cracked 
  • Extremities with hypoplastic fingers and toes
Our diagnosis based on the ultrasound findings was ichthyosis. The pregnancy was terminated at 30 weeks of gestations.

Images 1,2: Image 1 shows a thickened, Harlequin lips. Image 2 shows a cracked skin on the fetal face.

Ichtyosis_1
Ichtyosis_2

Images 3,4,5: Images shows cracks in the skin. Transverse view of the fetal abdomen on the image 4 shows a thickened skin with a crack indicated by arrow.

Ichtyosis_3
Ichtyosis_4
Ichtyosis_5

Images 6,7: Image 6 shows hypoplastic fingers. Image 7 shows the foot with hypoplastic toes, note the thickness of the foot dorsum.

Ichtyosis_7
Ichtyosis_6

Images 8,9: Fetal face, note large skales, severely everted eye lids - ectropion, Harlequin lips.

Ichtyosis_8
Ichtyosis_9

Images 10,11: Image 10 shows a detail of the skin on the neck. Image 11 shows a hand with hypoplastic fingers.

Ichtyosis_10
Ichtyosis_12

Image 12: Both feet, short toes, extremely thick dorsum.

Ichtyosis_11

References

1. Kudla M, Timmerman D. Prenatal Diagnosis of Harlequin Ichthyosis Using 3-and 4-Dimensional Sonography.J Ultrasound Med. 2010;29:317-319.
2. OMIM, GeneReviews; http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene∂=li-ar

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