Infants with harlequin ichthyosis often experience an excessive loss of fluids dehydration and develop life-threatening infections in the first few weeks of life. It used to be very rare for affected infants to survive the newborn period. However, with intensive medical support and improved treatment, people with this disorder now have a better chance of living into childhood and adolescence.
Mutations in the ABCA12 gene cause harlequin ichthyosis. The ABCA12 gene provides instructions for making a protein that is essential for the normal development of skin cells. This protein plays a major role in the transport of fats lipids in the outermost layer of skin the epidermis.
Other mutations lead to the production of an abnormally small version of the protein that cannot transport lipids properly.
A loss of functional ABCA12 protein disrupts the normal development of the epidermis, resulting in the hard, thick scales characteristic of harlequin ichthyosis. This condition is inherited in an autosomal recessive pattern , which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Genetics Home Reference has merged with MedlinePlus. The surviving children display dry, reddened skin, which may be covered by large thin scales, and sparse hair.
Physical development may be delayed by the enormous calorie needs their skin function demands, but mental and intellectual developments are expected to be normal.
Harlequin ichthyosis demands a meticulous skin care regimen to keep the skin moisturized and pliable and to prevent cracking and fissuring that may lead to infection. Because most of the fatalities from this condition occur in the first few days of life, many of the successes attributed to etretinate use in the medical literature may be equally due to the high quality of care in the immediate newborn period and to a less severely affected newborn.
Some newborns with harlequin ichthyosis will not survive, even with the best of care, because of the severity of their condition. Download a PDF version of this information. Why are the images hidden by default? Can I change this? They may not be downloaded or re-used for any purpose. This information is provided as a service to patients and parents of patients who have ichthyosis.
It is not intended to supplement appropriate medical care, but instead to complement that care with guidance in practical issues facing patients and parents. All issues pertaining to the care of patients with ichthyosis should be discussed with a dermatologist experienced in the treatment of their skin disorder.
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This site is in-development and may not reflect the final version. Preview the new GARD site. Other Names:. Ichthyosis congenita, Harlequin fetus type; Harlequin fetus. Congenital and Genetic Diseases ; Skin Diseases. Summary Summary. Symptoms Symptoms. Showing of 23 View All. Flat nose. Recessed nasal ridge. Eyelid turned out. Abnormal hearing. Frequent respiratory infections. Multiple respiratory infections. Susceptibility to respiratory infections.
Outward turned lips. Decreased joint mobility. Decreased mobility of joints. Limited joint mobility. Limited joint motion. Clouding of the lens of the eye. Cloudy lens. Duplication of bones of the toes. Extra finger. Respiratory impairment. Self-injurious behaviour. Premature sudden cardiac death. Drooping lower lip.
Outward turned lower lip. Premature delivery of affected infants. Preterm delivery. Bulging eye. Eyeballs bulging out. Prominent eyes. On year later, complete remission of the arthritis of the right knee was obtained without any limitation or side effects; no other joints have been involved in the meantime. Acitretin was progressively tapered, due to the improvement of the skin conditions, in particular eclabium and ectropion, and stopped at 10 months of age.
Patient 1: Clinical presentation at birth a ; Swelling of the right knee b , mimicking a septic arthritis, at 3 months of life. His whole body was covered by collodion-like membranes, thicker in the scalp, lower limbs and upper arms were flexed, contracted and covered by a thickened skin with multiple fissures. He presented also ectropion and deformity of the auricles. In the suspicion of congenital ichthyosis, the baby was referred to our Unit, where a skin biopsy and a molecular testing were performed.
Moreover the baby presented sepsis due to Enterococcus faecalis and bronchitis, requiring antibiotic therapy, since the admission to our Unit. Histological and genetic exams confirmed respectively the diagnosis of autosomal recessive congenital ichthyosis, sustained by the genomic variants c. Such mutations in ABCA12 determine the p. Leu75His rs , p. ArgTer rs , p. Cys55Tyr, p. AspTyr rs and p. GlyArg variants, respectively, at a protein level. The p.
Leu75His e p. ArgTer variants were due to paternal segregation. We promptly started oral therapy with acitretin 1.
After the discharge the baby manifested recurrent respiratory infections, which required multiple courses of antibiotics and glucocorticoids.
Transient relief was initially provided by short oral ibuprofen courses. After 2 months from the start of the therapy we documented the complete clinical and ultrasound remission in all the injected sites, except the persistence of both ankle swelling, due to diffuse tenosynovitis of the anterior and lateral compartments.
To date the child is still under follow-up, an additional injection procedure and methotrexate administration have been planned in the early future.
The baby did not manifest side effects related to both treatments. Patient 2 Swelling of the hands a and ankles b and c at 2 years of life. Harlequin Ichtyosis is an autosomal recessive genetic disorder due to the mutation of the ABCA12 gene in the chromosomal region 2q This gene belongs to a superfamily of ATP-binding cassettes, involved in the transport of biomolecules across the cell membrane, in the differentiation of keratinocytes and in the formation of the epidermal lipid barrier [ 4 , 5 , 6 , 7 , 8 ].
Mutations are classified as homozygous same mutation in both alleles or compound heterozygous different mutations on each allele [ 9 ]. Ominous outcome is usually associated with homozygous mutations. Our patients were carriers of a compound heterozygosity.
However, some children with HI show no mutations of the ABCA12 gene, suggesting that the genetic basis underlying HI is still far from to be clear [ 9 ]. In HI babies, skin is markedly thickened, the hard stratum corneum cracks soon after birth and leads to deep erythematous fissures delimiting geometric skin plates, with alopecia, ectropion, eclabium, and flattened ears.
Dehydration, hindered thermoregulation, increased metabolic demands, feeding disorders, respiratory distress, fingers fixed in flexion by tight skin and increased risk of infection may occur [ 1 , 10 ].
Skin of survivors evolves to generalized erythema and scaling, often with associated palmoplantar keratoderma. Developmental delay is frequently described as well [ 9 ]. The first line therapy of HI is oral retinoids and should be started early as much as possible [ 11 , 12 ]. Concerning the drug therapy, acitretin at the dose of 0. Only few case reports exist [ 1 , 15 ]. Sitek et al. However, our infants developed a precocious JIA, a pediatric chronic inflammatory disease, rarely reported in HI patients so early in the life.
Chan et al. The clinical improvement of erythema and arthritis was not associated with the parallel improvement of the hyperkeratosis and scaling.
Authors conclude the report warned about erosive arthritis, as an adverse event associated with etretinate therapy. To date this side effect of etretinate administration is not reported in the literature. The first line therapy for JIA was started with ibuprofen. Clement et al. Authors recommended to adequately treat JIA, because the because the reduction of mobility worsens contracture and joint swelling, accentuates skin lesions and increases the risk of infection.
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