Epidermolysis bullosa (EB) may be more common in the Netherlands than previously assumed, a long-term Dutch study suggests.
Results showed that EB now has a higher prevalence — the number of cases present in a particular population at a given time — than had been thought. Notably, EB simplex (EBS) is the most common type of this disorder in the country.
The findings highlight the need for specialized medical care for EB patients, the researchers said.
“These epidemiological data help to understand the extensive need for (specialized) medical care of EB‐patients and is invaluable for the design and execution of therapeutic trials,” the team wrote.
The study, “Novel insights into the epidemiology of epidermolysis bullosa (EB) from the Dutch EB Registry: EB more common than previously assumed?,” was published in The Journal of the European Academy of Dermatology and Venereology.
EB describes a group of rare skin disorders that lead to blistering of the skin. Previous epidemiological studies in the Netherlands have reported varying and inconclusive figures for EB, being mostly based on clinical features or molecular defects.
To provide accurate data, researchers from the Center for Blistering Diseases at the University Medical Center Groningen, in the Netherlands, conducted epidemiological analyses of well-characterized groups of patients registered in the Dutch EB Registry between 1988-2018.
The study included a total of 464 Dutch patients from 287 families. Diagnosis of EB was based on clinical features, skin biopsies, and genetic testing.
As of Dec. 31, 2018, the incidence of EB in the Netherlands was 41.3 cases per one million live births, with a total of 5,830,469 live births. Meanwhile, the point-prevalence, meaning the prevalence at a specific point in time, was 22.4 per million people out of a total Dutch population of 17,282,163.
Genetic testing confirmed the disease in 90.5% of cases — 420 patients from 254 Dutch families. The researchers found no disease-causing mutations in 22 patients, but most still had their EB subtype determined by imaging approaches.
As for genetic inheritance of EB, 304 individuals from 149 families (65.5%) showed dominant inheritance, meaning that a mutation in one of the two copies of a person’s genes — one inherited from each biological parent — is enough for EB to develop.
The remaining 160 patients from 138 families (34.5%) had a recessive form of EB — meaning both copies of the gene are defective. This can be the result of consanguineous parents. Of note, consanguineous parents are those who are related as second cousins or closer; their children have a higher risk of genetic diseases.
Regarding types of EB, 45.7% of individuals were diagnosed with EBS, 18.8% with junctional EB (JEB), 34.7% with dystrophic EB (DEB), and 0.9% with Kindler’s syndrome (Kindler EB). Incidence was highest for EBS at 17.5 cases per million live births, and lowest for Kindler syndrome at 0.5 per million live births. Similarly, point‐prevalence also was highest for EBS at 11.9 and lowest for Kindler syndrome at 0.2 per million population.
Specifically, EBS was found in 212 patients from 108 families. Dominant EBS was more common than recessive EBS (90.1% vs. 9.9%). Six genes were associated with EBS. In 81% of patients with recessive EBS, a homozygous mutation — meaning in both gene copies — was found, associated in most cases with parental consanguinity.
JEB was present in 87 patients from 72 families, with mutations in six genes implicated. Most JEB patients had a recessive form of the disease (94.3%). From these, 43.9% carried a homozygous mutation also derived from consanguineous parents in most cases. The remaining five patients (5.7%) had a dominant mutation in the ITGB4 gene.
DEB was identified in 161 patients from 103 families. Dominant DEB was more common than recessive DEB (67.1% vs. 32.9%). A homozygous mutation was identified in 35.8% of patients, with the vast majority (94.7%) having consanguineous parents.
In two patients with Kindler syndrome, the scientists found compound heterozygous mutations — two different mutations in each gene copy — in FERMT1. The other two patients had clinical features of the disease but no mutations were found.
Diagnosis could not be genetically confirmed in 18 EBS patients (8.5%), 12 of those with JEB (13.8%), and also 12 of the patients with DEB (7.5%).
During the study period, 73 patients died (15.7%); their average age at death was 22.9 years. Among these patients, 72.6% died as a direct consequence of the disease. In all, 68 had a recessive form of EB — 47 individuals with JEB, 16 with DEB, four with EBS, and one with Kindler syndrome — and five had a dominant form of the condition. The highest mortality rate was seen in JEB patients, with 90% of those with severe JEB dying in the first year of life from disease‐related complications.
Although this study was performed in a Dutch center with a high level of expertise, the researchers said their estimate had a risk of underestimating EB cases, particularly those of mild disease that may be monitored by general practitioners.
“The epidemiological outcomes of EB in the Netherlands are high, attributed to a high detection rate in a well‐organized set‐up, indicating that EB might be more common than previously assumed,” the researchers wrote.
“This study emphasizes the importance of thorough reporting systems and registries worldwide,” the team concluded.
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