Harlequin ichthyosis is a keratinization disorder due probably to cutaneous lipid anomalies. It is characterized by hyperkeratosis forming plates and grooves that look like Harlequin's costume. Infants with Harlequin ichthyosis are usually born prematurely and are encased in thick, hard, armor-like plates of cornified skin separated by deep fissures that severely restrict movement. Most infants with Harlequin ichthyosis are born as collodion babies that are born with a taut, shiny, translucent or opaque membrane that encases the entire body and lasts for days to weeks. The taut skin results in deformation of facial features and microcephaly. Affected infants are at risk for life-threatening complications in the postnatal period, such as respiratory distress, dehydration, electrolyte imbalance, temperature instability, feeding problems, and bacterial infections, often with fatal consequences. They usually die within the first weeks of life. However, improved survival into childhood and adolescence has been achieved with intense supportive care and systemic retinoid therapy in the neonatal period. Patients who survive manifest a debilitating, persistent ichthyosis.
Prenatal diagnosis for malignant keratoma had been performed by fetal skin biopsy and electron microscopic observation at 19-23 weeks estimated gestational age. Harlequin ichthyosis is very rare with an incidence of about 1 in 300.000 births.
Harlequin ichthyosis is transmitted as an autosomal recessive trait. The vast majority of individuals with this disorder have mutations in ABCA12 gene, including partial-gene deletions. ABCA12 gene encodes for a protein that belongs to a subfamily of ATP-binding cassette (ABC) transporters. These transporters carry many types of molecules across cell membranes. In particular, the ABCA12 protein plays a major role in transporting lipids in cells of the epidermis. This lipid transport appears to be essential for normal development of the skin. Thus, mutations in this gene probably lead to an absence of ABCA12 protein or the production of an extremely small version of the protein that cannot transport lipids properly. A lack of lipid transport causes numerous problems with the development of the epidermis before and after birth. Specifically, it prevents the skin from forming an effective barrier against fluid loss (dehydration) and infections, and leads to the formation of hard, thick scales characteristic of harlequin ichthyosis.
Selim et al. (2000) described a baby male born to an Egyptian family with consanguineous marriage (first cousin) with six siblings four (3 females and 1 male) of whom died because of Harlequin icthyosis (HI). The boy was born at 35 weeks showing HI. His weight at birth was 2630 grams. His face showed grotesque features with everted eye lids, flat nose, and prominent nostrils. The entire body was covered by cracked thick armor like skin, and hands and feet look matted. He died few days after delivery. The history of the these cases, and of other cases included in their study, led Selim et al. (2000) to indicate that the disease is inherited as an autosomal recessive manner in all affected infants, and found to be associated with a fatal outcome in all cases.
[See: Egypt and Sudan > Selim et al., 2000].
Selim et al. (2000) described a consanguineous Sudanese family (first cousin) with two HI infants (one female and one male). The male infant died three minutes after delivery. The baby girl is the first HI case in this family. She had thick fissured thickened skin all over the body and the toes of feet and fingers of the hands were clumped. She had flat ears and prominent nasal opening and a flat nose. There were no eye lashes or eye brows. The mouth was fish shaped. She was treated with Etretinate (Tigason; 1mg/1kg body weight/day). She began to improve 10 days from the start of treatment. The treatment was maintained and the thick armor like scales were replaced by a fairly smoother skin, the ectropion became less, the mouth had a better appearance and hands and feet improved. She died at age of 3.5 months because of chest infection [See also: Egypt > Selim et al., 2000].
Larguèche et al. (2009) reported the case of a male infant born at 40 weeks' gestational age to consanguineous parents who were first cousins. The infant was covered with massive thick, waxy, plate-like scales and deep fissures. There was striking facial distortion including severe eclabium and ectropion. The baby died at two days of age.
Bastaki et al. (2017) studied Emirati congenital ichthyosis patients. They described a 5-month-old male suffering from thick, shiny, scaly skin, single bilateral palmar creases, bilateral sole swelling, and small toes. He had a similarly affected older brother and two paternal aunts with a history of skin dryness. His parents were healthy and not related. WES uncovered 3 heterozygous mutations in the ABCA12 gene of both brothers: two known missense mutations (c.2785C>T, pArg929Cys; c.6852G>C, p.Glu2284Asp) and a novel frameshift (c.335_336delC, p.Ser112tyrfs*25). The frameshift was predicted to result in nonsense mediated decay and both missense variants were predicted to be functionally damaging. The father was found to carry both heterozygous missense mutations while the mother had the heterozygous frameshift variant. The authors also described a 1.5-year-old male child born to healthy consanguineous parents. He suffered from generalized scaling of the skin, erythroderma, eclabium, severe ectropion, inguinal hernia and retractable testes. His growth parameters were below the third centile and he suffered recurrent skin infections. He was diagnosed with Harlequin Ichthyosis and an ABCA12 screening revealed a homozygous c.2487dupT (p.Arg830Glufs*16) mutation. The duplication was predicted to result in nonsense mediated decay and both parents were found to be heterozygous carriers.
To contribute with your findings to the content of this record, please fill the CTGA Database Information Submission Form and email it, along with supportive documents, to firstname.lastname@example.org.