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Pediatric Oncall Journal

Lamellar Ichthyosis in a Female Neonate with a Novel Mutation on TGM1 Gene 12/20/2021 00:00:00

Lamellar Ichthyosis in a Female Neonate with a Novel Mutation on TGM1 Gene

Ana Francisca Henriques Cardoso1, Flávia Oliveira Belinha2, Ana Ratola3, Raquel Henriques3.
1Pediatric Department, Centro Hospitalar de Leiria, Leiria, Portugal,
2Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal,
3Maternidade Daniel de Matos, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

Ana Francisca Henriques Cardoso, Rua Camilo Korrodi, nº 34, B1.2, Leiria, Portugal.
Congenital ichthyosis comprise a group of genetic disorders caused by mutations in the keratinocyte differentiation and consequent disruption of the skin barrier function. Autosomal recessive congenital ichthyosis is a heterogeneous, non-syndromic subgroup characterized by a defect in skin cornification, hyperkeratosis, scaling and erythroderma. The term collodion baby encompasses neonates wrapped at birth in a shiny collodion membrane that peels away in the first weeks of life and is gradually replaced by the definitive phenotype. We report a case of a collodion baby that progressed to a lamellar ichthyosis (LI) with a novel mutation of the TGM1 gene that has not been reported in the literature. This case highlights the need to expand the spectrum of TGM1 mutations in order to understand the etiopathogenesis of LI.
congenital ichthyosis, collodion baby, TGM1.
Congenital ichthyosis comprise a group of genetic disorders caused by mutations in the keratinocyte differentiation and consequent disruption of the barrier function of skin leading to increased vulnerability to infections and dehydration.1
Case Report
The subject of this report is a female neonate, born to non-consanguineous parents at 33 gestational weeks. The mother is a 40-year-old G4P3 with a history of Crohn’s disease treated with adalimumab and azathioprine. There is no family history of skin diseases. Cesarean delivery 3 days after preterm premature rupture of membranes (previous cesarean section). At birth, the newborn was covered in a parchment-like membrane with underlying erythroderma. Her extremities were edematous and fingers were in a fixed contracture due to the tight collodion membrane (Figure 1). A few hours after birth, her skin revealed several fissures and digital constrictions. Associated findings included ectropion, eversion of lips, flattening of nose and ears and limitation of joint movements (Figure 2). The neonate’s Apgar scores were 9 and 10 at 1 and 5 minutes, respectively. There were no other associated congenital anomalies. Because of the impaired skin integrity, the newborn was transferred to a neonatal intensive care unit.

Figure 1. Collodion baby that subsequently progressed to a lamellar ichthyosis phenotype.
<b>Figure 1.</b> Collodion baby that subsequently progressed to a lamellar ichthyosis phenotype.

Figure 2. Bilateral ectropion and eclabium at 2 days old.
<b>Figure 2.</b> Bilateral ectropion and eclabium at 2 days old.

The patient remained clinically stable with a good peripheral perfusion and vital signs within the normal range for the gestational age. She was monitored in a high-humidity incubator (relative humidity 80%) with, close monitoring of body temperature and adequate fluid and electrolyte replacement. She needed nutritional support through a nasogastric tube. Topical emollients were consistently applied and the dermatologist opinion was taken who did not recommend a biopsy because the diagnosis was essentially clinical. As advised by the ophthalmologist artificial tears were applied to prevent drying of eyes. During the first few days postpartum, the skin status dynamically changed and evolved with resolution of the scales following the next 3 weeks. As the ectropion and eclabium improved she was discharged from the intensive care unit at the age of 26 days with recommendations for being followed up in pediatric consultation. The severity of scaling and erythema kept fluctuating over time. At age of 10 months, the patient presented with xerosis and hyperpigmented brown scales (Figure 3). Genetic analysis revealed a variant of uncertain significance that has not been described in the literature: a homozygous mutation in transglutaminase-1 (c.1252G>C (p.Asp418His)) located on chromosome 14q11.2. Parents did not want to perform genetic analysis but signed the consent for case reporting and image publication.

Figure 3. Multiple lamellar brown scales remained over the patient’s trunk and axillar areas.
<b>Figure 3.</b> Multiple lamellar brown scales remained over the patient’s trunk and axillar areas.

ARCI is a major subgroup of cornification disorders with a widely varied presentation and overlapping phenotypes. These infants are usually born prematurely and covered in a collodion membrane with fissuration areas and ulcerated lesions.6 Presumptive diagnosis emerge at the time of birth and, a few weeks later, CB evolves into a subtype of ARCI, such as CIE/LI or it may even resolve spontaneously.
Here we reported the case of a LI female neonate that was born prematurely with a collodion membrane covering her entire body surface. Initially, she presented with a shiny taut skin that dried and flaked because of chest expansion. The thickening of the skin and pulling of the tissues around are responsible for the appearance of ectropion and eclabium, which are typical clinical findings and facilitates the diagnosis. In this case, the collodion membrane was later replaced by hyperkeratotic membrane with brownish thick scales evolving into a pattern suggestive of LI. Sequencing of the TGM1 gene revealed c.1252G>C (p.Asp418His), a novel mutation that has not been yet reported in the literature classified as a variant of uncertain significance.
The dominant cause of ARCI (especially of LI subtype) are mutations in TGM1 gene but mutations in other genes have been reported.4 Fischer et al. study detected mutations in at least 1 of these genes in 78% of 520 families with ARCI (TGM1 in 32%, NIPAL4 in 16%, ALOX12B in 12%, CYP4F22 in 8%, ALOXE3 in 5% and ABCA12 in 5%).7
Patients with mutations in the TGM1 gene develop a more complicated phenotype compared to those with other mutations. Numerous studies have tried to demonstrate correlation between mutations in TGM1 and clinical features. However, due to the clinical heterogeneity, to date no significant association has been found.8
These infants are at risk to hypernatremic dehydration, disrupted thermoregulation, cutaneous and systemic infections and failure to thrive secondary to poor feeding.6
Symptomatic treatment of LI includes maintaining stable body temperature, ensuring fluid and electrolyte balance and hypercaloric intake, monitoring of infections, pain assessment, administering baths, emollient creams, ocular lubricants and preventing the development of contractures in the distal phalanges.9
The outcome and prognosis of a CB depends on the complicationswhich may arise in the neonatal period and underlying genetic mutations. These patients need regular follow-up with a multidisciplinary team and genetic counseling must be offered to parents in order to explain the etiology of the disorder.9
Recognizing the clinical presentation of congenital ichthyosis is crucial to provide an early and adequate treatment to affected neonates. Furthermore, this case highlights the need to expand the spectrum of TGM1 mutations in order to better understand the etiopathogenesis of LI.
Compliance with Ethical Standards
This study did not receive funding.
Conflict of Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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Cite this article as:
Cardoso A F H, Belinha F O, Ratola A, Henriques R. Lamellar Ichthyosis in a Female Neonate with a Novel Mutation on TGM1 Gene. Pediatr Oncall J. 2023;20: 106-108. doi: 10.7199/ped.oncall.2023.15
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