What are the other Names for this Condition? (Also known as/Synonyms)

• JBS (Johanson-Blizzard Syndrome)
• Nasal Alar Hypoplasia, Hypothyroidism, Pancreatic Achylia and Congenital Deafness

What is Johanson-Blizzard Syndrome? (Definition/Background Information)

• Johanson-Blizzard Syndrome (JBS) is a very rare condition that affects multiple parts of the body. Many symptoms are present at birth or early childhood
• 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
• Johanson-Blizzard Syndrome can becaused 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

(Source: Johanson-Blizzard Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Johanson-Blizzard Syndrome? (Age and Sex Distribution)

• Johanson-Blizzard Syndrome is a rare congenital disorder. The presentation of symptoms may occur at or following the birth of the child
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Johanson-Blizzard Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Johanson-Blizzard Syndrome is an inherited condition
• Currently, no other risk factors have been clearly identified for JBS

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Johanson-Blizzard Syndrome? (Etiology)

Johanson-Blizzard syndrome is caused by mutations (changes) to the 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

(Source: Johanson-Blizzard Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Johanson-Blizzard Syndrome?

The signs and symptoms of Johanson-Blizzard Syndrome vary, but may include:

• Abnormality of the nail
• Agenesis of permanent of teeth
• Anasarca
• Aplasia cutis congenita of scalp
• Atrial septal defect
• Calvarial skull defect
• Clinodactyly of the fifth finger
• Clitoral hypertrophy
• Colonic diverticula
• Convex nasal ridge
• Cryptorchidism
• Fair hair
• Frontal upsweep of hair
• Hypocalcemia
• Hypoplastic nipples
• Hypothyroidism
• Joint laxity
• Micropenis
• Rectovaginal fistula
• Single transverse palmar crease
• Situs inversus totalis
• Small for gestational age
• Sparse scalp hair
• Strabismus
• Urethrovaginal fistula
• Ventricular septal defect

Very frequently present symptoms in 80-99% of the cases:

• Abnormal hair pattern
• Alopecia
• Exocrine pancreatic insufficiency
• Failure to thrive
• Intrauterine growth retardation
• Malabsorption
• Short nose
• Underdeveloped nasal alae

Frequently present symptoms in 30-79% of the cases:

• Abnormality of the vagina
• Absent lacrimal punctum
• Anal atresia
• Anemia
• Anteriorly placed anus
• Delayed eruption of teeth
• Delayed skeletal maturation
• Hypoproteinemia
• Intellectual disability
• Lacrimation abnormality
• Microdontia
• Oligodontia
• Sensorineural hearing impairment

Occasionally present symptoms in 5-29% of the cases:

• Abnormality of the cardiac septa
• Abnormality of the nares
• Cholestasis
• Dextrocardia
• Diabetes mellitus
• Dilated cardiomyopathy
• Edema
• Hepatic failure
• Hydronephrosis
• Hypoplasia of penis
• Hypospadias
• Microcephaly
• Muscular hypotonia

(Source: Johanson-Blizzard Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Johanson-Blizzard Syndrome Diagnosed?

Johanson-Blizzard Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Johanson-Blizzard Syndrome?

The complications of Johanson-Blizzard Syndrome may include:

• Failure to thrive
• Severe malnutrition
• Severe multifunctional abnormalities
• Death in infancy, is known to occur

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Johanson-Blizzard Syndrome Treated?

The treatment of Johanson-Blizzard syndrome focuses on the specific symptoms that are present in each individual.

• Those with pancreatic insufficiency may require pancreatic enzyme supplements (e.g., oral pancreatin) to promote proper absorption of fats and other necessary nutrients
• Vitamin supplements may also be needed to prevent or treat vitamin deficiencies that may result from malabsorption due to pancreatic insufficiency. A special diet with easily-absorbed, high-protein supplements may also be prescribed to ensure that total nutritional requirements are met
• Although these therapies usually lead to improved nutrient absorption and weight gain, most affected children still remain smaller and shorter than average for their ages
• A surgery for pancreas removal (pancreatectomy) and with islet autotransplantation (TPIAT) should be used only as a last resort for patients with severe symptoms of pancreatitis
• 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

(Source: Johanson-Blizzard Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Johanson-Blizzard Syndrome be Prevented?

Currently, Johanson-Blizzard Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Johanson-Blizzard Syndrome? (Outcomes/Resolutions)

• The severity of the symptoms in Johanson-Blizzard syndrome (JBS) varies. While some patients may develop life-threatening complications during infancy, other have a less severe disease
• Although intellectual disability does occur, in some cases, intelligence is normal. Hearing loss or deafness may be present at birth or may develop later during life
• Growth deficiency associated with JBS may occur because of malabsorption and exocrine pancreatic insufficiency
• Without treatment, impairment of the pancreas and malabsorption can progress to cause life-threatening complications like infections and malnutrition
• Specific treatment of the pancreatic insufficiency and hypothyroidism can result in a better outlook
• 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

(Source: Johanson-Blizzard Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Additional and Relevant Useful Information for Johanson-Blizzard Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/