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Prevalence of epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) is unknown, but more than 40 cases have been reported to date.

Onset of blistering is usually as early as birth, whereas muscular dystrophy manifests between infancy and adulthood, with a median age of onset of 9.5 years. Blisters are often hemorrhagic and heal with mild atrophic scarring and rare milia formation. Associated findings comprise markedly dystrophic nails, and focal keratoderma of the palms and soles. Extracutaneous involvement is usually present, including enamel hypoplasia with premature tooth decay, blistering in the oral cavity, pharynx and, rarely, larynx and trachea with inspiratory stridor and breathing difficulties requiring tracheotomy. Slowly progressive weakness of the head and limb muscles appears between the first year and the fourth decade of life and may confine the patient to a wheelchair. Additional neurological symptoms (ptosis, oculobulbar muscle weakness and fatigability) indicative of a myasthenic syndrome have been described in some patients. Mucosal involvement including urethral mucosae is common. Cardiomyopathy may be associated and, in rare cases, pyloric atresia.

EBS-MD is caused by mutations in the PLEC gene (8q24) encoding plectin. Plectin deficiency can be demonstrated in skin and muscle by analysis with specific antibodies.

Diagnosis is based on the mode of transmission, histopathological findings, and clinical presentation. Immunofluorescence mapping demonstrates lack of immunoreactivity for plectin and a plane of cleavage deep within the basal pole of the basal keratinocytes. Transmission electron microscopy shows intraepidermal split formation with lamina densa and lucida, and hemidesmosomes on the floor of the blister. Genetic testing demonstrates biallelic loss-of-function pathogenic variants in PLEC coding for plectin.

Differential diagnosis is of other types of EBS and disorders with congenital skin blistering.

Prenatal diagnosis should be offered to affected families in which the pathogenic variant/s have been previously diagnosed.

The disorder is autosomal recessive and genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy.

There is no specific treatment available, treatment is symptomatic with wound management and general support.

From a prognostic point of view, immunohistochemical recognition of EBS-MD in infancy is particularly important, since in some patients the associated muscular dystrophy may not become apparent until later in childhood or adulthood. EBS-MD may have a fatal outcome.