Case report describes boy with JEB, two other rare diseases

Other genetic disorders were Angelman syndrome and autosomal recessive deafness type 57

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A young boy in Spain was evaluated for developmental delay and found to have three different genetic diseases: junctional epidermolysis bullosa (JEB), Angelman syndrome, and autosomal recessive deafness type 57.

While having more than one genetic disease is not uncommon, researchers estimated that having both JEB and Angelman syndrome may occur in as few as one in one billion babies in the world.

In such complex situations, it is important that doctors keep track of new symptoms that may arise over time because they may help reach a more accurate — or even new — diagnosis. 

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“Only patient-centered medical assistance and the coordination of the different specialists could guarantee the best quality of life and comfort in these complex situations,” the researchers wrote.

Their report, “Coexistence of junctional epidermolysis bullosa, autosomal recessive deafness type 57, and Angelman syndrome: A case report,” was published in the journal Clinical Case Reports.

The 9-month-old boy was born with small fluid-filled bumps, blisters, and scabs all over his body. Based on these symptoms, doctors suspected he might have epidermolysis bullosa, a disease that causes skin to become fragile and blister easily.

A close look at the area between the epidermis (the top layer of skin) and the dermis (the layer below the epidermis) revealed low levels of laminin 332, a protein that strengthens the skin but often is missing or does not work properly in people with JEB.

JEB is a type of epidermolysis bullosa that causes blisters between the epidermis and the dermis. Most cases of JEB result from mutations in genes coding for parts of laminin 332. Sometimes, mutations occur in COL17A1, a gene that codes for part of a collagen protein that also helps to strengthen the skin.

Mutation in the COL17A1 gene

Genetic testing revealed that the boy carried two copies of a mutation in the COL17A1 gene. The mutation, called c.3766 + 1G>A, is a known cause of intermediate JEB, a milder form of the disease. His parents, who were related by blood, also carried the mutation in one gene copy. Two mutated copies are needed for JEB to develop.

At age 2 months, the boy started having problems growing and gaining weight (failure to thrive). At 8 months, he experienced trouble breathing and had to be hospitalized because of laryngotracheomalacia, a congenital softening of voice box tissues, and croup — a condition that causes swelling in the airways and creates breathing problems.

One month later, the boy was evaluated at the pediatric neurology department because he was not developing as expected. He could not sit up on his own, and certain physical features such as weak facial muscles, low-set ears, and a small jaw became noticeable.

At 12 months, the child was found to have hearing loss in both ears. At 17 months, the boy still had difficulty sitting upright, but could hold his head steady. He was social and playful, but was behind in using his hands and had not yet started talking. He was underweight and had a small head size.

To look for a cause underlying the developmental delay and the hearing loss, the researchers revisited the boy’s genetic information. They ran an analysis through the exome, which is the entire portion of a genome that provides instructions for making proteins.

The analysis revealed a deletion of a region located in chromosome 15 that is a known cause of Angelman syndrome, a genetic disease that can cause developmental delay and problems with speech and balance.

First such case in junctional epidermolysis bullosa?

According to the researchers, this is the first case reporting on JEB coexisting with Angelman syndrome. This might be very rare, and “the combined occurrences of both events would be approximately 0.97 cases per billion births,” they wrote.

In addition, the analysis revealed a mutation, called c.883C>T/p.Pro295Ser, in both copies of the PDZD7 gene. This gene codes for a protein that is present in the hair cells of the ear, which convey sound information from the ear to the brain.

PDZD7 has been associated with deafness in fewer than 20 families. Both his mother and father carried one copy of the mutation in the PDZD7 gene.

“Ongoing evaluation of patient signs and symptoms enables reanalysis of exome data sequencing, the diagnosis of coexisting diseases, and can facilitate access to new treatments,” the researchers wrote.

Despite ongoing research on gene therapy for Angelman syndrome, this type of treatment could be challenging in this particular case due to the presence of three different genetic diseases, the researchers noted.