Ichthyosis Prematurity Syndrome

Abstract

Ichthyosis prematurity syndrome (IPS) is a rare autosomal recessive congenital disorder characterised by premature birth, congenital ichthyosis and neonatal respiratory distress. IPS is caused by pathogenic variants of the SLC27A4 gene encoding fatty acid transporter protein 4 (FATP4), resulting in skin barrier dysfunction [1]. Herein, we present, to our knowledge, the first Australian case of IPS in a patient of Indonesian heritage.

A male infant of Indonesian heritage was born at 29 + 3 weeks gestation with diffuse scaling. He was born to healthy non-consanguineous parents, with his mother gravida 1, parity 1. Routine antenatal screening was unremarkable, but polyhydramnios was identified 1 day prior to delivery. Labour was induced following prolonged rupture of membranes with suspected chorioamnionitis, and he was ultimately born via Caesarean section due to breech positioning and foetal distress.

His birthweight was 1882 g, and his APGAR scores at 1, 5 and 10 minutes were 1, 6 and 6, respectively. Widespread clay-like vernix was noted affecting the scalp, face, back and upper and lower extremities (Figure 1), with occlusion of the auditory canals. Soon after birth, he developed respiratory distress, with chest X-ray showing ill-defined multilobar opacities compatible with pulmonary oedema (Figure 2). He had transient eosinophilia of 12% (normal: < 5%). Serum immunoglobulin E (IgE) was not tested. No abnormal findings were reported on abdominal X-ray, renal ultrasound and cranial ultrasound. Histology of the exfoliated scale demonstrated anucleate keratin.

He was transferred to the neonatal intensive care unit, placed on continuous positive airway pressure (CPAP) ventilation and administered surfactant. CPAP was transitioned to low-flow oxygen on day 19 postnatally. Other postnatal complications included jaundice, Staphylococcus aureus-associated conjunctivitis and anaemia of prematurity. Breastfeeding was supplemented by enteral nutrition.

The patient was discharged after 10 weeks (corrected age 39 + 4 weeks gestation), with a continuing requirement for low-flow oxygen until 5 months of age. Newborn hearing screen test results were abnormal but normalised at 4 months. His skin was managed with white soft paraffin, with spontaneous shedding of scale. At 8 months, there was complete resolution of ichthyosis (Figure 2), and development was within normal limits.

Genetic testing confirmed the presence of germline, compound heterozygous variants of the SLC27A4 gene. The first was a pathogenic deletion of exons 8 to 10, previously implicated in IPS [2, 3]. The second was a single nucleotide change at c.986C>T (p.Thr329Met) of uncertain significance, which has been previously reported in the literature as a homozygous variant in patients with clinical IPS [4].

While respiratory distress may also be seen in collodion and Harlequin presentations, in IPS it is thought to be primarily due to aspiration of keratin debris in amniotic fluid rather than restricted chest expansion [5, 6]. Eosinophilia and polyhydramnios (as seen in our patient), along with raised IgE levels, have also been reported in IPS [4]. Clinicians should consider genetic counselling for parents given the germline nature of the diagnosis. While the vernix-like scaling often resolves with simple topical management, patients may be left with persistent mild generalised ichthyosis, atopic manifestations or other skin abnormalities such as follicular hyperkeratosis, alopecia and hypohidrosis [3, 7]. Although the long-term prognosis is generally favourable, rare cases resulting in mortality have occurred [4].

The authors have nothing to report.

Written informed consent has been obtained.

D.F.S. has received consulting fees from Galderma, AbbVie, Pfizer, Amgen, Novartis, Janssen, Leo Pharma, Bristol Myers Squibb, Eli Lilly, iNOVA, Ego Pharmaceuticals and Sun Pharma, and received material support from Candela Medical and Heine Optotechnik. D.F.S. is an editorial board member of the Australasian Journal of Dermatology and a co-author of this article. To minimise bias, he was excluded from all editorial decision-making related to the acceptance of this article for publication. G.X.L., K.C. and J.P.P. have no conflicts of interest to report.