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Ichthyosis congenita, harlequin type: A case report and a brief review of

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Article · January 2016

DOI: 10.4103/2319-7250.187888

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CASE REPORT

Ichthyosis congenita, harlequin type: A case report

and a brief review of literature
Veeresh V Dayavannavar, Soumya Jagadeesan1, Shashidhar Veerappa2, Anees Aisha3
Departments of Dermatology, 2Pediatrics and 3Obstetrics and Gynaecology, ESIC Medical College, Gulbarga, Karnataka,
1
Department of Dermatology, Amrita Institute of Medical Sciences, Kochi, Kerala, India

ABSTRACT

Harlequin ichthyosis (HI) is the most severe type of congenital ichthyosis, and it is extremely rare. It is inherited in
an autosomal recessive fashion. Although previously thought to be lethal, recently there have been increased reports of
prolonged survival, following improved supportive care and judicious use of systemic retinoids. We report a new case of
HI in an infant born of a consanguineous marraige who succumbed on the 5th day of birth despite intensive supportive care,
a short review of literature regarding the condition is also presented.

Key words: Harlequin fetus, harlequin ichthyosis, ichthyosis congenita, acitretin

INTRODUCTION the whole body surface area with intervening deep‑red

fissures [Figure 1]. Ectropion, eclabium, flattening of

H arlequin ichthyosis (HI) is the most severe form

of congenital ichthyosis. The infants are born
with dense plaque‑like scales forming a horny shell
around the body resulting in an alarming appearance.
The disease is usually lethal in the neonatal period,
but survival is reported to be longer in recent
years.[1] We report a new case of HI in an infant born
of a consanguineous marraige who succumbed on the
5th day of birth despite intensive supportive care, a
short review of literature is also presented.
CASE REPORT
A preterm female baby was born to a 22‑year‑old
primigravida at 33 weeks of gestation by spontaneous
vaginal delivery. The antenatal period was uneventful,
and the last ultrasonogram performed at 28 weeks of
gestation did not reveal any abnormality. The baby
cried shortly after birth. Her birth weight was 1.37 kg,
length 42 cm, and head circumference 28 cm. On
examination, there were thick armor‑like plates covering
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ears and nose were noted with distorted facial features.
Flexion contracture of the arms, legs, and digits was
present, and the nails were hypoplastic. All natural
orifices were patent. Other vital parameters were
normal. An ultrasonogram of the abdomen revealed
no significant abnormality. With this distinctive
presentation, a diagnosis of HI was made. The parents
were first cousins, and there was no history of similar
disorders in the family. Karyotyping and mutational
analysis was offered but was refused by the parents.
The infant was started on broad spectrum antibiotics
with appropriate intravenous fluids and shifted to a
humidified incubator in the Neonatal Intensive Care
Unit [Figure 2]. Nasogastric feeding was initiated.
Topical antibiotics and emollients were applied as
a part of skin care and the skin was cleansed with
ADDRESS FOR CORRESPONDENCE
Dr. Soumya Jagadeesan,
Department of Dermatology, Amrita Institute of Medical Sciences,
Ponekkara PO, Kochi ‑ 682 041, Kerala, India.
E‑mail: soumyavivek@gmail.com
This is an open access article distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non‑commercially, as long as the
author is credited and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com

DOI: How to cite this article: Dayavannavar VV, Jagadeesan S, Veerappa S,

10.4103/2319-7250.187888 Aisha A. Ichthyosis congenita, harlequin type: A case report and a brief
review of literature. Indian J Paediatr Dermatol 2016;17:319-21.

© 2016 Indian Journal of Paediatric Dermatology | Published by Wolters Kluwer ‑ Medknow 319

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Dayavannavar, et al.: A case of harlequin ichthyosis
Figure 1: Infant at birth, showing the hyperkeratotic plates with intervening
red fissures, eclabium, distorted facial features, and contractures of hands
and feet
normal saline. Protective eye pads and antibacterial
eye drops were used as a part of eye care. Despite the
supportive care, the child developed respiratory failure
and succumbed on the 5th‑day postdelivery. A post-
mortem examination was suggested but refused by the
relatives due to social reasons.
DISCUSSION
HI is a rare autosomal recessive keratinization
disorder. The incidence of this disorder is around
1:300,000.[2] No racial or sexual predilection has been
reported. The genetic and biochemical basis is poorly
understood. Abnormalities of the skin are linked to the
abnormal structure and function of lamellar granules,
whose function is to secrete lipids that maintain the
skin barrier. Harlequin infants either do not have
these granules or have defective ones, which results
in massive loss of water between the layers of skin.
Loss‑of‑function mutations of ABCA12 gene, coding
for a membrane‑based lipid transporter protein,
responsible for the formation and function of lamellar
granules, is found to be present in many studies.[3]
The first description of this disorder is thought to be
from the diary of Rev. Oliver Hart, of Charleston, South
Carolina, who described these features in 1750.[4] The
clinical presentation of the neonate is “alarming” with
a distinctive hyperkeratotic coat of armor covering
the entire body surface with red fissures and skin
patterning resembling a harlequin’s costume, hence
the name. Movement is restricted, and respiratory
insufficiency results from limited chest expansion
and sometimes coexistent skeletal deformity. The
absence of effective sucking causes feeding difficulties
which may lead to hypoglycemia, dehydration, and
renal failure. The infants are also at risk of infections
beginning in the skin but do not show signs of it due
320
Figure 2: Infant shifted to a humidified incubator in the Neonatal Intensive
Care Unit and started on intravenous fluids and nasogastric feeds
to poor temperature control. Therefore, these children
are at great risk during the neonatal period and may
die shortly after birth as happened in our case.[5]
Management of HI in the early neonatal
period involves care in a humidified incubator,
thermoregulation, care of skin and mucosae, adequate
nutrition, management of infections and pain
control besides medical treatment. A humidified
incubator with temperature control helps to prevent
transcutaneous loss of water and heat from the body.
Bland emollients, if gently applied to the skin surface
area will also help to prevent water loss and improve
the barrier function. Frequent application of saline
compresses helps in softening the hardened skin.
Ryle’s tube feeding and intravenous fluids should be
initiated to take care of the nutritional requirements
and to regulate the fluid‑electrolyte balance. Care of
the eye with frequent use of lubricants to protect the
conjunctiva and other measures to prevent exposure
keratitis is required. Frequent cultures should be sent
and the child must be kept in a sterile environment to
minimize the risk of infections. If there is obstruction
due to hyperkeratosis, surgical intervention may be
needed. A multidisciplinary team approach is required
to manage the condition effectively.
Medical treatment with systemic retinoids in the
neonatal period itself is reported to cause accelerated
shedding of the hyperkeratotic plates within the first
few weeks itself. Etretinate was the first retinoid used
later replaced by acitretin which is now the most
commonly used drug, started in the first few days
after birth at a dose of 0.5–2.5 mg/kg.[6] Therefore,
advances in the neonatal intensive care with judicious
use of systemic retinoids are found to be effective in
Indian Journal of Paediatric Dermatology | Vol 17 | Issue 4 | Oct-Dec 2016
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Dayavannavar, et al.: A case of harlequin ichthyosis
prolonging survival in recent years. Rajpopat et al.
assessed clinical outcomes of 45 cases of HI and
reported an overall survival rate of 56% ranged from
10 months to 25 years.[1,5] We had planned to start
the infant on acitretin shortly but the condition
worsened, and the infant expired before this could
be performed. Moreover, survival may also depend
on the type of mutations, victims with homozygote
mutations having less chance of survival as compared
to compound heterozygotes.[1]
Prenatal diagnosis would be the first step for early
detection of the disease, especially in those with a
family history of similar disorders, consanguinity,
etc. A fetal skin biopsy may be helpful as early as at
18 weeks of gestation, and chorionic villous sampling
and amniocentesis have also been reported to be useful.
Ultrasound examination may suggest the diagnosis as
early as 17 weeks of gestation, especially in patients
with other afflicted members in the family.[7] The
findings described to be helpful in prenatal sonological
diagnosis are the absence of typical ear morphology,
atypical facial dysmorphism, large open mouth,
absence of typical nasal morphology, partitioned cystic
formations in front of eyes, thick skin, minimal fetal
movement with stiff limbs in a semiflexed position,
limb anomalies with hypoplastic fingers, toes and short
phalanges, clubfoot, shriveled hands that do not open,
hyperechogenic amniotic fluid, and the absence of
associated visceral anomalies.[8] However, ultrasound
might not be helpful in all cases due to delayed
phenotypic expression and rarity of the disease, due
to which it is often missed, as happened in our case.[7,9]
The importance of detailed genetic counseling and
prenatal diagnosis cannot be overemphasized, especially
when parents plan for next offspring. The newer
DNA‑based molecular techniques and the new generation
sonological advancements have enabled earlier and
accurate diagnosis of genodermatoses such as HI.[10]
CONCLUSION
We report a new case of HI who did not survive
despite intensive supportive care. This case adds to
our collective knowledge about this rare entity.
Indian Journal of Paediatric Dermatology | Vol 17 | Issue 4 | Oct-Dec 2016
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Declaration of Patient Consent
The authors certify that they have obtained all
appropriate patient consent forms. In the form the
patient(s) has/have given his/her/their consent for his/
her/their images and other clinical information to be
reported in the journal. The patients understand that
their names and initials will not be published and
due efforts will be made to conceal their identity, but
anonymity cannot be guaranteed.
Financial Support and Sponsorship
Nil.
Conflicts of Interest
There are no conflicts of interest.
REFERENCES
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Hellstrom‑Pigg M, et al. Harlequin ichthyosis: A review of
clinical and molecular findings in 45 cases. Arch Dermatol
2011;147:681‑6.
2. Arikan II, Harma M, Barut A, Harma MI, Bayar U. Harlequin
ichthyosis: A case report and review of literature. Anatol J
Obstet Gynecol 2010;1:1‑3.
3. Kelsell DP, Norgett EE, Unsworth H, Teh MT, Cullup T,
Mein CA, et al. Mutations in ABCA12 underlie the severe
congenital skin disease harlequin ichthyosis. Am J Hum Genet
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4. Waring JI. Early mention of a harlequin fetus in America. Am J
Dis Child 1932;43:442.
5. Layton J. A review of harlequin ichthyosis. Neonatal Netw
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6. Digiovanna JJ, Mauro T, Milstone LM, Schmuth M, Toro JR.
Systemic retinoids in the management of ichthyoses and related
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Babaeipour‑Divshali M. Harlequin ichthyosis: Case report.
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