Harlequin Fetus Really Lethal ? A Case Report of Prolonged Survival
Harlequin fetus is a rare type of congenital ichthyosis which is usually considered to be lethal. We report a Chinese baby girl born with the abnormality who has survived to 4 years old at the time of report. The literatures on the possible prenatal diagnosis, recent advance in management & prolonged survival of harlequin fetuses are also reviewed. Our case appeared to be the seventh case of prolonged survival beyond neonatal period that has ever been reported.
Keyword : Harlequin fetus; Prolonged survival
Harlequin fetus is a rare type of congenital ichthyosis and is usually considered to be lethal. We report a baby girl born with the abnormality who has survived to 4 years old at the time of this report. The literature on the possible prenatal diagnoses, recent advances in management and prolonged survival of harlequin fetuses are also reviewed.
The affected baby girl weighing 2835 gm at birth was the second child of non-consanguineous Chinese parents. The mother had three previous pregnancies. The first two pregnancies had ended up as first trimester abortions. She gave birth to a full term female baby in her third pregnancy by Caesarean section. This baby was found to suffer from congenital ichthyosis and died shortly after birth. The mother was thus referred to our prenatal diagnostic clinic during her fourth pregnancy. Ultrasound examination at 21 weeks gestation showed the fetus with flexion contractures of all four limbs. Repeat ultrasound at 30 weeks showed an abnormal fetus with thickened skin, eclabion, smooth facial contour and diminished fetal movements suggestive of a Harlequin fetus. Prenatal counselling and prenatal diagnosis including skin biopsy were offered but was declined by the couple. The baby girl was delivered by lower segment Caesarean section for previous caesarean section and cephalopelvic disproportion at 38 weeks of gestation with good Apgar score.
At delivery, the baby was noted to be encased in a thick and whitish membrane with extensive deep red fissures (Fig. 1). The skin had an offensive odour. There was severe ectropion of the eyelids and eclabion of the mouth. The ears were flattened and adhered to the side of the head. The nose was flattened and the nostrils was shredded with thick yellowish crust. She had sparse scalp hairs, eyebrows and eyelashes. The toes and fingers were hypoplastic with flexion contracture and they were bound together by thick scaly skin. Her chest expansion was also limited. Other systems were unremarkable.
The baby was nursed in an incubator with optimal humidification and tube feeding was started on the first day of life. There was initially mild feeding intolerance which subsequently improved. She required supplemental oxygen up to 30% until 4 weeks of life. Initial skin management included daily bath and gentle debridement with emulsifying ointment. Urederm cream was applied to the whole body 4 times per day. The ectropion was treated with 1 % chloramphenicol eye ointment. Her skin gradually softened and the thick skin plaques turned yellowish brown, then became separated and was shredded off gradually, leaving a red surface covered with whitish thin scaly skin. The eclabion improved with softening of the perioral skin and she was able to suck from the bottle by the fifth day of life.
Skin biopsy was performed at 1 week of life. Histopathologic examination showed markedly thickened stratum corneum about 20 times the thickness of stratum malphigii. There was focal papillomatosis and mild parakeratosis. The appearance of the granular layer was variable ranging from normal, flattened, or event absent in a certain small area. Apparent follicular plugging was also noticed. The dermal tissue was unremarkable (Fig. 2). Electron microscopic examination showed crystal like structures resembling cholesterol deposited in corneoytes.
There was an episode of staphylococcus aureus skin infection during the second week of life, which responded to antiseptic bath. She had also episodes of eye sepsis controlled with antibiotic eyedrops. The eyes were then protected by methylcellulose eyedrops 4 times per day.
At 6 weeks of age the skin condition had greatly improved and she was able to maintain her body temperature in an open cot. By that time, most of the thick scaly skin had dropped off but there was continual shedding of thin scales all over the body. Ectropion and eclabion were also partially reversed. The digits however were still covered by thick skin (Fig. 3).
Oral etretinate treatment was only started at 11 weeks of age. This treatment was offered to the baby but was initially strongly objected by the parents. The parents' attitude was extremely negative because of the gross external abnormalities of the baby and their previous unpleasant experience. Later, they signed off the baby despite the gradual skin improvement. The oral etretinate given at 2.5 mg daily (i.e. 0.75 mg per kilogram body weight per day) was well tolerated and serial liver function and renal function monitoring were within normal limit.
She was transferred to a convalescent hospital for rehabilitation and training at 14 weeks. Subsequently, she has been admitted four times to acute paediatrics ward because of skin infection, rotavirus gastroenteritis and acute bronchiolitis. She has remained healthy otherwise. Her weight gain was fair after the first six months and her body length and body weight had stayed around 3rd centile since. Developmental milestones was appropriate at the time of report. The skin condition has improved further with decreased desquamation and increased motility. (Fig. 4)
Harlequin fetus is a rare condition with less than 100 cases reported in the world's literature since it was first described by Reverend 0 Hart in his diary in 1750.1 The condition does not seem to have any racial nor sexual predilection. Familial cases and parental consanguinity had been reported and an autosomal recessive mode of inheritance was previously suggested.2
The elder sibling of our patient was also affected. However, there was no other family history nor parental consanguinity to ascertain the mode of inheritance. Like our patient, successful prenatal diagnosis using ultrasound guided fetal skin biopsy has been described.3,4 Fetal skin biopsies showed premature hyperkeratosis, most marked around the hair follicles and sweat ducts with formation of hyperkeratotic plugs before 20 weeks of gestation in the affected fetus. In contrast, epidermis of control fetuses consisted of squamous epithelium only with minimal keratinisation. Ultrasonic features in utero like our patient's have also been described.5
The clinical picture of our patient is typical with thick armour-like skin splitted by deep fissures and severe ectropion and eclabium. She has shown a significant degree of spontaneous improvement in the first 3 months of life before etretinate was administered. The clinical course was similar to other reported cases with recurrent skin infections but major complications such as septicaemia, osteomyelitis were not experienced in our case.
Etretinate was first used to treat harlequin fetuses by Lawler & Peiris in 1985.6 Its exact action is not known but retinoids have been shown to control the differentiation and proliferation of keratinising and non-keratinising epithelia. So far, there were 5 reported cases so treated with variable outcome.7-11 In 3 cases, there were significant improvement and the patients survived at the time of report which resembled our patient. One showed significant improvement but died at 16 days of life. The other one case, similar to our patient, there was already improvement in skin condition before etretinate was started. One harlequin fetus even survived without using retinoid. Hence, etretinate probably played a permissive role in the management of these babies. The mainstay of treatment is still meticulous skin care and maintenance of fluid balance and provision of adequate calorie intake.
Most harlequin fetuses died in the first days or weeks of life, with death attributed to septicaemia, pulmonary infection, mechanical restriction of respiration and poor feeding as well as excessive fluid loss. Prolonged survival has been achieved in 5 cases (see Table) with intensive supportive measures, emollients and oral etretinate. Nevertheless, most patients still had significant morbidity with persistent skin peeling, skin infection and failure to thrive. Our patient also suffered from similar complications. Though the developmental milestones were reported to be normal in 3 of the cases, the long term outcome of these babies remained questionable.
Previously, harlequin fetuses were considered to be lethal and paediatricians often adopt a negative approach in the management of these babies. Aggressive supportive care will probably enhance survival and etretinate may improve the quality of life by ameliorating the skin condition. As paediatricians, should we adopt a more positive attitude towards this condition from now on?
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2. Tor Shwayder. All about ichthyosis. Paediatr Clin North Am 1991;38(4):835-57.
3. Elias S, Mazur M, Simpson JL. Prenatal Diagnosis of harlequin ichthyosis. Clin Genet 1980;17:275-80.
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8. Roberts U. Long term survival of a harlequin fetus. J Am Acad Dermatol 1989;21 :999-1006.
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10. Buxman MM, Goodkin PE, Fahrenbach WH, Dimond RL. Harlequin ichthyosis with epidermal lipid abnormality. Arch Dermatol 1979;115:189-93.
11. Prasad RS, et at. Management & follow up of Harlequin siblings. Br J Dermatol 1994;130:650-3.
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