Search for a rare disease
Other search option(s)
Junctional epidermolysis bullosa, generalized severe
Junctional epidermolysis bullosa, Herlitz-type is a severe subtype of junctional epidermolysis bullosa (JEB, see this term) characterized by blisters and extensive erosions, localized to the skin and mucous membranes.
ORPHA:79404Classification level: Disorder
- Epidermolysis bullosa letalis
- JEB, generalized severe
- Junctional epidermolysis bullosa generalisata gravis
- Junctional epidermolysis bullosa, Herlitz type
- Junctional epidermolysis bullosa, Herlitz-Pearson type
- Prevalence: 1-9 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: Q81.1
- OMIM: 226700
- UMLS: C0079683
- MeSH: -
- GARD: 2153
- MedDRA: -
Reported incidence ranges are 1/2,500,000 and 1/1,470,000 live births in the United States and Italy, respectively, and 1/250,000 live births in the Netherlands. According to data from U.S. and Italian EB registries, about 20% of patients with JEB have the more severe Herlitz type.
The condition is present at birth. Exuberant granulation tissue is a characteristic manifestation, which usually arises within the first several months to one to two years of life, and may involve the skin (around nail folds, in a mask-like distribution on the face, and at sites of friction, such as shoulders and buttocks), and the upper airways. Involvement of mucous membranes may affect the entire gastrointestinal (GI) tract, genitourinary tract, and respiratory tract to the bronchioles. However, the most significant and frequent mucosal lesions are those in the upper part of the GI and respiratory tracts. The numerous erosions and ulcerations of the oral mucosa severely hamper feeding, and involvement of the laryngotracheal mucosa, manifesting as hoarseness, dyspnea and stridor, may lead to acute respiratory failure requiring tracheostomy. Other constant features include nail anomalies with paronychia, various degrees of onychodystrophy and nail shedding. Dental abnormalities, when survival enables their observation, include regularly marked hypoplasia or complete absence of enamel. Frequent ocular lesions comprise corneal blisters, erosions and scarring and ectropion formation. Failure to thrive is an almost constant finding in JEB-H, and multifactorial anemia is also common.
JEB-H is caused by mutations in one of the three laminin-332 coding genes: LAMA3 (18q11.2), LAMB3 (1q32) and LAMC2 (1q25-q31). In most cases, null mutations are found on both alleles of the causative gene.
In addition to the finding of a cleavage plane located within the lamina lucida of the cutaneous basement membrane zone, a negative immunofluorescence staining for laminin-332 is typical of JEB-H. However, in rare cases the staining is strongly reduced and thus does not enable differentiation of JEB-H from JEB non-Herlitz (see this term). In these cases, genetic testing, showing null mutations in one of the three genes encoding laminin-332, is necessary to confirm the diagnosis.
Genetic testing allows prenatal diagnosis for pregnancies at increased risk.
The condition follows an autosomal recessive pattern of inheritance.
Prognosis is poor and most JEB-H patients die in the first few years of life, with the major causes of death being failure to thrive, respiratory failure, sepsis, and pneumonia. In addition, squamous cell carcinomas may arise in a minority of JEB-H patients (4.5% according to data from the U.S. National EB Registry).
- Summary information
- Russian (2012, pdf)
- Emergency guidelines
- Français (2012, pdf)
- Anesthesia guidelines
- English (2011, pdf)
- Review article
- English (2010)
- Clinical genetics review
- English (2018)