Skin ulcers in newborn girl lead to diagnosis of rare form of EBS
KLHL24-related subtype linked to potential heart risks: Case study
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A baby girl born with severe skin erosions and ulcers was diagnosed with a rare form of epidermolysis bullosa simplex (EBS) that carries the risk of heart disease, according to a case study that highlights the distinct skin features and potential heart risks of this EBS subtype.
Caused by mutations in the KLHL24 gene, this rare disease type is characterized by areas of skin loss, early scarring, changes in skin color and hair follicles, and cardiomyopathy, a disease of the heart muscle.
The researchers are reporting the baby’s case to bring attention to the “atypical neonatal features” of KLHL24-associated EBS, noting that it “may mimic other conditions and [emphasizing] the importance of early genetic diagnosis” when it occurs.
“This case is presented to highlight the neonatal findings of KLHL24-associated EBS, which diverge from the typical picture of EB in neonates, making early diagnosis difficult,” the researchers wrote in detailing the baby’s care.
“Recognizing KLHL24-associated EBS is important, as cardiac screening is recommended starting in childhood to identify and manage the potential cardiomyopathy promptly,” the team wrote.
The case study, “Neonatal KLHL24-Associated Epidermolysis Bullosa Simplex: Clinical Presentation and Genetic Confirmation of a Rare Skin Fragility Syndrome,” was published in the journal Pediatric Dermatology by a team of U.S. researchers.
Most cases of EBS are caused by mutations in genes that encode keratin, a tough, fibrous protein that forms the primary material of hair, nails, and the outer layer of skin. Faulty keratin leads to skin that’s fragile and easily damaged, blistering with friction or minor trauma.
Heart muscle affected in this rare EBS subtype
Defects in the KLHL24 gene have recently been shown to cause an EBS subtype marked by cardiomyopathy, in which the heart muscle becomes enlarged and weakened. Mutations in this gene, which is equally active in skin and heart cells, boost the function of a protein that drives the excessive keratin degradation.
Individuals with KLHL24-related EBS — now termed EBS intermediate with cardiomyopathy — typically experince blistering and areas of skin loss at birth, especially on the limbs. As these patients grow, they may develop thin, star-shaped scars, changes around hair follicles, temporary small cysts (milia), and sometimes involvement of mucous membranes.
Skin color changes, often in swirling or patchy patterns, tend to appear in childhood. Although skin fragility often eases with age, ongoing features can include abnormal nails, localized areas of loss of skin elastic tissue, and hair loss. Cardiomyopathy also can occur.
In this report, researchers at Children’s Hospital Colorado detailed the case of a newborn girl who was transferred to the hospital one day after birth for evaluation of widespread skin erosions and ulcerations affecting her scalp, limbs, and torso. She was born at 38 weeks (full term is about 40 weeks) following a pregnancy complicated by gestational diabetes and pre-eclampsia, or persistent high blood pressure in the mother. The pregnancy was also marked by excess amniotic fluid and infection of the membranes.
On examination, the newborn was otherwise stable, but had deep, irregular skin ulcers on her arms, hands, legs, and feet, along with early scarring. Additional findings included small scalp and abdominal erosions and plaques, with hair follicle dimpling on the thighs and abdomen. A single blister was noted, and her nails and mucous membranes appeared normal.
Due to concerns about infection, she was started on antibiotics and antiviral therapy. Further testing ruled out infections and neonatal lupus, which can be the cause of skin symptoms.
A skin biopsy showed fibrosis, or scarring, in the dermis, an inner layer of skin underneath the epidermis, the outer layer of skin. Doctors also observed a small separation at the junction between the epidermis and dermis.
“While scarring and fibrosis are findings of dystrophic EB, they are not typical of other forms of EBS,” the team noted.
As new blisters developed in areas of friction, clinicians pursued genetic testing for epidermolysis bullosa, which revealed a mutation in the KLHL24 gene. Over the following days, the infant’s skin lesions healed with scarring, and the plaques evolved into areas of follicular atrophy, marked by the shrinkage and reduction in the number of hair follicles.
By 9 months, most of baby’s skin lesions had resolved
The baby was discharged home at 13 days of life, and with her family, returned to their hometown in Mexico, according to the researchers.
By 9 months of age, her condition had improved significantly, with most lesions resolved, leaving thinning skin and characteristic pigmentation changes, the team noted.
Cardiac evaluation was not completed during the initial hospitalization, as the genetic diagnosis was confirmed after discharge.
When patients exhibit skin fragility, [star-shaped] scarring, and [hair follicle] atrophy, the diagnosis of KLHL24-associated EBS should be considered. … The timely diagnosis of this subtype of EBS is critical due to its association with [potential heart disease].
The researchers said this case highlights the need for heightened testing in individuals with fragile skin.
“When patients exhibit skin fragility, [star-shaped] scarring, and follicular atrophy, the diagnosis of KLHL24-associated EBS should be considered,” the researchers wrote. “The timely diagnosis of this subtype of EBS is critical due to its association with [cardiomyopathy].”
The team noted that “continued cardiology follow-up is recommended … throughout childhood and adolescence” in these cases.
