What is Harlequin Ichthyosis (HI) and is it fatal?
Harlequin ichthyosis (HI) is a rare genetic skin disorder. Infants with this condition are born encased in a very hard, yellow thick skin (Collodion Membrane) covering most of their bodies with large, diamond-shaped plates which are separated by deep cracks. These skin abnormalities affect the shape of most of the organs, restricting movement of the body. The risk of death is high during the neonatal period, babies being susceptible to severe temperature dysregulation, feeding difficulties, infections and respiratory problems. When they survive, the collodion membrane sheds after a few weeks and transforms into severe erythroderma with severe scaling and persistent ectropion. Other clinical features associated with HI are keratoderma, failure to thrive, short stature, malformed ears and digits, and nail deformities and alopecia.
What is the prevalence of HI and how is it diagnosed?
HI is very rare; but its exact incidence is still unknown. Recent study in year 2014, estimated the incidence as 1 in 300,000 live births. A diagnosis of HI is usually made by clinical examination in the newborn. Prenatal ultrasonography, particularly 3-dimensional ultrasonography, may show features suggestive of HI. This has been particularly helpful in antenatal diagnosis of infants with no family history of harlequin ichthyosis. Two-dimensional ultrasonography can also demonstrate features of HI but not until late in the second trimester, when enough keratin buildup is present to be sonographically detectable.
What causes HI?
In year 2005, the cause of HI was traced to genetic changes (mutation) in ABCA12 Gene. The ABCA12 gene provides instructions for making a protein known as an ATP-binding cassette (ABC) transporter which is very important for the normal development of skin cells. This protein plays a major role in the transport of lipids in the outermost layer of skin (epidermis). Mutations in ABCA12 gene disrupt the function of ABCA12 protein which further disrupts the normal development of the epidermis, resulting in the hard, thick scales.
How does HI run in the family and what is the risk for having the affected baby?
HI is inherited as an autosomal recessive condition, which means that there should be two mutated copies of the gene (one coming from mother and one from father) in each cells. So the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene (known as carrier of autosomal recessive condition), but they typically do not show signs and symptoms of the condition. Risk of having affected babies in autosomal recessive disorder is 25%. So it is very important to offer Genetic counseling to the family to inform them the risk of recurrence and advise genetic testing.
Can HI prevented and what options are available for testing HI in parents and pregnancy?
HI cannot be prevented but it is possible to diagnose or recognize it early in pregnancy by prenatal diagnosis (PND) which can be done using amniocentesis or Chorionic Villus sampling which involve removing some of the amniotic fluid or chorionic Villi surrounding the developing foetus to identify if there is a mutation in ABCA12. This allows the family to decide if they wish to continue or terminate the pregnancy. It is also feasible to do preimplantation genetic diagnosis (PGD) if the family do not want to go through the trauma of medical termination of pregnancy after PND. PGD is a relatively new way to look even earlier into the genes of the developing embryo. In PGD a normally fertile couple will choose to undergo in-vitro fertilization and then test each of the embryos for a genetic disease, before they are transferred to the mother’s womb. PGD is really a hope for the parents who have already had a child with genetic disease like HI to have a healthy baby. Igenomix, New Delhi provide this advanced technology to help the couple with the family history of any single gene disease to have healthy baby. It is really important to test the affected baby and parents for ABCA12 gene before going ahead or planning for PND or PGD to know the mutation they are carrying. Affected baby is always tested first followed by carrier screening for the parents. Igenomix, New Delhi can provide this testing using product CGT one in which ABCA12 gene can be analyzed.
What is the management approach for HI?
There is no cure for the disease but it can be managed with treatment. In the past the disease was considered fatal. But with advanced technology improved survival rate has been achieved with intensive neonatal care. In the neonatal period, management requires a multidisciplinary approach (ophthalmologists, dermatologist, surgeons, dieticians, Clinical Geneticist, genetic counselors and psychologists). Survivors have a normal life expectancy but may develop severe skin disease with eye complications, with delayed developmental milestones, motor and social skills. Infants are discharged from the hospital when their cutaneous symptoms are improving, feeding and weight gain are established, and they are free of infection. There are families with one or more children with Harlequin ichthyosis who live happy and relatively normal life. Some Survivors of this disease (Nusrit Shaeen, Stephanie turner and Hunter Steintiz) are now living into adolescence.
How can the families be supported and educated?
It is very important to provide social and psychological support for the parents/caregivers. It should be advised 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 to the parents/caregivers. Counsel them that how can they recognize signs of infection. As this condition can have devastating medical and social consequences, Parents may wish to communicate with other families with the same problem. Patient organizations and support groups are available in several countries to provide support to families.
