Disease Profile

Johanson-Blizzard syndrome

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of Onset

Infancy

ageofonset-infancy.svg

ICD-10

Q87.8

Inheritance

Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other Names (AKA)

JBS; Nasal alar hypoplasia, hypothyroidism, pancreatic achylia and congenital deafness

Categories

Congenital and Genetic Diseases; Digestive Diseases; Endocrine Diseases;

Summary

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.[1]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Cause

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.[2] 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. 

Treatment

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, highprotein 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.[3]

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.[3]

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal hair pattern
Abnormal distribution of hair
0010720
Alopecia
Hair loss
0001596
Exocrine pancreatic insufficiency
Inability to properly digest food due to lack of pancreatic digestive enzymes
0001738
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Malabsorption
Intestinal malabsorption
0002024
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Short stature
Decreased body height
Small stature

[ more ]

0004322
Underdeveloped nasal alae
Underdeveloped tissue around nostril
0000430
30%-79% of people have these symptoms
Abnormal vagina morphology
0000142
Absent lacrimal punctum
0001092
Anal atresia
Absent anus
0002023
Anemia
Low number of red blood cells or hemoglobin
0001903
Anteriorly placed anus
0001545
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

0000684
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Hypoproteinemia
Decreased protein levels in blood
0003075
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Lacrimation abnormality
Abnormality of tear production
0000632
Microdontia
Decreased width of tooth
0000691
Oligodontia
Failure of development of more than six teeth
0000677
Sensorineural hearing impairment
0000407
5%-29% of people have these symptoms
Abnormal cardiac septum morphology
0001671
Abnormality of the nares
Abnormality of the nostrils
0005288
Cholestasis
Slowed or blocked flow of bile from liver
0001396
Death in infancy
Infantile death
Lethal in infancy

[ more ]

0001522
Dextrocardia
Heart tip and four chambers point towards right side of body
0001651
Diabetes mellitus
0000819
Dilated cardiomyopathy
Stretched and thinned heart muscle
0001644
Edema
Fluid retention
Water retention

[ more ]

0000969
Hepatic failure
Liver failure
0001399
Hydronephrosis
0000126
Hypoplasia of penis
Underdeveloped penis
0008736
Hypospadias
0000047
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Muscular hypotonia
Low or weak muscle tone
0001252
Percent of people who have these symptoms is not available through HPO
Abnormality of the nail
0001597
Agenesis of permanent teeth
Failure of development of permanent teeth
Missing teeth

[ more ]

0006349
Anasarca
0012050
Aplasia cutis congenita of scalp
0007385
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Autosomal recessive inheritance
0000007
Cafe-au-lait spot
0000957
Calvarial skull defect
Cranial defect
Skull defect

[ more ]

0001362
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Clitoral hypertrophy
Enlarged clitoris
0008665
Colonic diverticula
0002253
Convex nasal ridge
Beaked nose
Beaklike protrusion
Hooked nose
Polly beak nasal deformity

[ more ]

0000444
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Death in childhood
0003819
Fair hair
Blond hair
Fair hair color
Flaxen hair color
Light colored hair
Sandy hair color
Straw colored hair
Towhead (hair color)

[ more ]

0002286
Frontal upsweep of hair
Cowlick
Frontal Cowlick
Upswept frontal hair

[ more ]

0002236
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Hypocalcemia
Low blood calcium levels
0002901
Hypoplasia of the primary teeth
Decreased size of baby teeth
Decreased size of milk teeth
Small baby teeth
Small milk teeth
Underdevelopment of baby teeth
Underdevelopment of milk teeth

[ more ]

0006334
Hypoplastic nipples
Small nipples
0002557
Hypothyroidism
Underactive thyroid
0000821
Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes cystic fibrosis, Shwachman-Diamond syndrome, Pearson Marrow-Pancreas syndrome, partial pancreatic agenesis (for congenital exocrine pancreatic insufficiency), oculodentodigital dysplasia (for hypoplasia of the alae nasi) and Adams-Oliver syndrome (for aplasia cutis congenita) (see these terms).
Visit the Orphanet disease page for more information.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn More

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Johanson-Blizzard syndrome. Click on the link to view a sample search on this topic.

          References

          1. Johanson-Blizzard Syndrome. NORD. 2013; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1089/viewAbstract. Accessed 11/30/2015.
          2. Zenker M. Johanson-Blizzard syndrome. Orphanet; July 2016; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=2315.
          3. Shelton CA & Whitcomb DC. Genetics and Treatments Options for Recurrent Acute and Chronic Pancreatitis. Curr Treat Options Gastroenterol. September, 2014; 12(3):359–371. https://www.ncbi.nlm.nih.gov/pubmed/24954874. Accessed 11/30/2015.
          4. Hurst JA & Baritser M. Johanson-Blizzard syndrome. J Med Genet. January, 1989; 26(1):45–48. https://www.ncbi.nlm.nih.gov/pubmed/2645405.
          5. Godbole K, Maja S, Leena H & Martin Z.. Johanson-blizzard syndrome. Indian Pediatr. May 8, 2013; 50(5):510-2. https://www.indianpediatrics.net/may2013/510.pdf.