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Chu et al. Rare Dis Orphan Drugs J 2023;2:2 https://dx.doi.org/10.20517/rdodj.2022.25 Page 3 of 10

CASE REPORT
Patient 1
Patient 1 was an 11-month-old boy, born at full term via elective Caesarean section, with a normal birth
weight of 2.875 kg. Antenatal history was unremarkable, including a normal routine second-trimester
structural ultrasound. He is the second son of non-consanguineous Chinese parents, and his elder brother
(2 years older) was reported to be healthy since birth. There is no contributory family history of skin and/or
other related conditions.

The initial presenting features were two small round superficial skin desquamative lesions over the buttock,
2 cm and 1 cm in diameter, respectively, noted upon newborn examination immediately after birth.
Subsequently, further extensive skin erosions developed all over the trunk and limbs, some spontaneously
with no apparent trigger, but most significantly over pressure sites, which corresponded to the locations of
blood pressure cuff application and blood sampling [Figure 1].

In view of the extensive dermatological lesions with desquamation and exposure of the underlying raw
dermal area, the baby was referred for clinical genetics evaluation and was transferred to the Neonatal
Intensive Care Unit (NICU) of a tertiary hospital on the first day of life, where dermatological, paediatric
surgical and plastic surgery burns unit support were available. Skin biopsy showed subepidermal blisters
with a completely detached blister roof, basket weave keratosis and mostly intact slightly thickened
epidermis. There were no features of inflammation, scarring, cytoid bodies, basal vacuolar degeneration, or
caterpillar bodies. Special staining showed focal areas with linear hyaline basement membrane along the
blister floor with no mucin deposition. Direct immunofluorescence was suboptimal due to completely
denuded epidermis but no staining of immunoglobulins, complements or fibrinogen. The anatomical
pathologist’s initial impression was a cell-poor subepidermal blistering disease, possible junctional type
epidermolysis bullosa.

Trio-based rapid whole exome sequencing (WES) was performed by the corresponding author’s team in the
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong. The results returned
positive with a turnaround time of 11 days. Compound heterozygous pathogenic variants in the FERMT1
gene were identified in patient 1. The first variant was FERMT1(NM_017671.4):c.811C>T p.(Arg271Ter),
inherited from his father; and the second variant was FERMT1(NM_017671.4):c.1718+2T>C, inherited from
his mother. Both variants had been previously reported in individuals with KS, and were classified as
pathogenic according to The American College of Medical Genetics and Genomics (ACMG) guidelines
(Richards et al., 2015) . The genetic diagnosis of KS and supportive findings were communicated with
[10]
dermatologists and anatomical pathologists, and both agreed that the clinical presentation and biopsy
features were compatible.

The baby continued to receive in-patient multidisciplinary care. Emollients and dressing were applied for
skin protection, and the dermatological condition gradually improved despite occasional scattered lesions
and blistering, mostly corresponding to pressure or friction. The ophthalmological assessment confirmed
no involvement of the eyes.

The early perinatal course was otherwise uneventful, except for transient respiratory distress after delivery
which required antibiotic coverage and heated humidified high-flow oxygen nasal cannula (HHHFNC) for
three days. However, soon after feeding started, the baby developed intermittent episodes of blood and
mucus in stool with no increase in inflammatory markers and no infective pathogen isolated, which
resolved when enteral feeding was withheld but recurred when feeding resumed. There was no consistent