Johanson-Blizzard syndrome (JBS) is a very rare condition that affects multiple parts of the body. The severity, signs and symptoms of JBS may vary among affected individuals. Many symptoms are present at birth or early childhood. Characteristic features include intestinal malabsorption of fats and other nutrients due to abnormal development of the pancreas (pancreatic insufficiency); failure to thrive, contributing to short stature; abnormalities of permanent teeth; distinctive skull and facial features; and/or varying degrees of intellectual disability. JBS can be caused by changes (mutations) in the UBR1 gene and is inherited in an autosomal recessive manner.The treatment focuses on the specific symptoms that are present in each individual and may include pancreatic enzyme supplements (e.g., oral pancreatin) and vitamin supplements.

UBR1 gene. This gene provides instructions to the body to produce a protein that is important for the function of the pancreas. This protein is produced in specific cells in the pancreas called acinar cells. Acinar cells are important because they help produce digestive enzymes which allow the pancreas to break down food and use the food products for growth (malabsorption). Because people with Johanson-Blizzard syndrome have a UBR1 gene that is not functioning correctly, the acinar cells of the pancreas are destroyed and the pancreas cannot break down fats and other nutrients as well. This leads to many of the symptoms of JBS such as slow growth.

Johanson-Blizzard syndrome is inherited in an autosomal recessive manner. This means that both copies of the UBR1 gene (one inherited from the mother and one inherited from the father) are not working in people who have JBS. Any future children with the same mother and father will have a 25% chance of having JBS.

UBR1 gene (one inherited from the mother and one inherited from the father) have a mutation and are not working.

Affected people inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

• 25% chance to be affected
• 50% chance to be an unaffected carrier like each parent
• 25% chance to be unaffected and not a carrier

For someone who has Johanson-Blizzard, they have a mutation in both copies of their UBR1 gene. When that individual goes to have children, they will automatically pass on one mutation to their child, making their child a carrier. The only way for the child to be affected is if their other parent is a carrier for Johanson-Blizzard syndrome and also passes on a copy of the gene with a mutation, resulting in the child inheriting two mutations in the UBR1 gene.

Individuals with hypothyroidism may need thyroxine hormone replacement therapy. Other abnormalities such as craniofacial, genitourinary, cardiac, and/or other malformations associated with the condition may be treated with surgery. Dental abnormalities may be treated with bonding agents, use of dentures, and/or other techniques. Hearing loss may be treated with hearing aids. Early intervention is important to ensure that children with JBS reach their full potential. Affected children may benefit from special remedial education, special social support, and other medical, social, and/or vocational services.

Life expectancy depends more in the pancreatic insufficiency and the malnutrition that may lead to death in infancy or early childhood, but for patients managed early with efficient pancreatic enzyme and vitamin supplementation, survival into adulthood is not rare.