Prenatal diagnosis of harlequin ichthyosis by ultrasonography: a case report

Abstract

Autosomal recessive congenital ichthyosis is a genetically and phenotypically heterogeneous group of skin disorders, including harlequin ichthyosis (HI), lamellar ichthyosis, and bullous congenital ichthyosiform erythroderma. HI is the most phenotypically severe autosomal recessive congenital ichthyosis associated with the mutation of the adenosine triphosphate-binding cassette subfamily A member 12 (ABCA12) gene. The clinical manifestations include generalized hyperkeratotic plaques and deep fissures, ectropion, eclabium, and contractures. However, the severe HI may easily be misdiagnosed as epidermolysis bullosa or syndromic ichthyosis. Meanwhile, no consensus exists about the best used in clinical trials or clinical practice when more elaborate scoring systems have been proposed to evaluate skin xerosis, palmoplantar keratoderma, and disease extension an accurate prenatal diagnosis is necessary. Until the ABCA12 gene was identified as the pathogenic gene, prenatal diagnosis of HI had been performed by the invasive techniques of fetal skin biopsy. Now, advances in ultrasound technology and fetal DNA-based analysis have replaced it. The mortality rate is markedly high and prompt; prenatal diagnosis of neonate HI is critical for appropriate perinatal and postnatal management. It is also essential to prepare parents for future pregnancies and reduce the family's physical and mental distress and financial burden. This report presents a rare case of harlequin ichthyosis diagnosed by the ultrasound and discusses the significance of prenatal ultrasound diagnosis and molecular diagnosis in the prenatal diagnosis of HI.

Deletion in Exon-20 of ABCA12 Gene Causing Harlequin Ichthyosis

“…3 Prenatal ultrasonographic features like eclabium (eversion of lips), ectropion (outturning of eyelid), contractures, and snowflake sign (floating skin particles in amniotic fluid) are indicators toward the diagnosis of HI; however, these are not detectable until the second trimester. [2][3][4] Affected babies are generally born premature and are encased in a markedly thickened and hard stratum corneum described as armorlike skin. Such thickened skin can cause pseudocontractures resulting in limited joint movements and impaired perfusion that can further lead to digital necrosis.…”

“…Most infants initially could be managed with liquid paraffin, topical eye lubricants/antibiotics, paracetamol for pain relief, and oral retinoids that help in shedding of the grossly thickened skin. [2][3][4]…”

Current Strategies for the Gene Therapy of Autosomal Recessive Congenital Ichthyosis and Other Types of Inherited Ichthyosis

“…The ultrastructure of lamellar bodies in HI cells is impaired due to the deficiency of intercellular lamellae in the stratum corneum [ 35 ]. Three-dimensional sonography construction can also be used to diagnose severe ARCI, including HI, by the presence of dense floating particles in amniotic fluid (“snowflake sign”), which indicates abnormal corneocyte shedding (disadhesion) [ 36 ].…”

Prenatal diagnosis of ichthyosis congenita gravis (Harlequin ichthyosis [HI]) using 3D sonography

“…Today, prenatal diagnosis is no longer performed by fetoscopy and skin biopsy 8 9 but by 3D sonography 6 10 11 12 13 14 and DNA analysis after amniocentesis or chorionic villus sampling 2 3 15 16 .…”

“…The detection of debris in amniotic fluid has also been described 19 . A much better representation of the clinical picture, especially of the fetal face, can be achieved with 3D sonography 6 10 11 12 13 14 . In particular, with the surface display in HDlive mode, conspicuous facial details, such as inverted eyelids, a hypoplastic nose, a typical open fish mouth with eclabium and macroglossia, can be displayed in a photograph-like manner ( Fig.…”