Johanson-Blizzard syndrome

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Other Names:

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

Categories:

Congenital and Genetic Diseases; Digestive Diseases; Endocrine Diseases; Congenital and Genetic Diseases; Digestive Diseases; Endocrine Diseases; Nervous System Diseases; Skin Diseases See More

Summary 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]

Last updated: 11/30/2015

Symptoms 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.

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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
Increased VLDL cholesterol concentration		0003362
Joint laxity	Joint instability Lax joints Loose-jointedness Loosejointedness [ more ]	0001388
Micropenis	Short penis Small penis [ more ]	0000054
Midline skin dimples over anterior/posterior fontanelles		0005498
Rectovaginal fistula	Abnormal connection between rectum and vagina	0000143
Septate vagina	Double vagina	0001153
Single transverse palmar crease		0000954
Situs inversus totalis	All organs on wrong side of body	0001696
Small for gestational age	Birth weight less than 10th percentile Low birth weight [ more ]	0001518
Sparse scalp hair	Reduced/lack of hair on scalp Scalp hair, thinning Sparse, thin scalp hair sparse-absent scalp hair [ more ]	0002209
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Urethrovaginal fistula		0008716
Vascular dilatation	Wider than typical opening or gap	0002617
Ventricular septal defect	Hole in heart wall separating two lower heart chambers	0001629

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Do you have updated information on this disease? We want to hear from you.

Cause 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.

Last updated: 12/31/2016

Inheritance Inheritance

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) have a mutation and are not working.^[1]^[2]

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.

Last updated: 1/25/2018

Treatment 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, 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.^[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]

Last updated: 11/30/2015

Prognosis Prognosis

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.^[1]^[4]

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.^[4]^[5]

Last updated: 3/8/2016

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

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 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

About Face International
51 Wolseley Street
Toronto, ON M5T 1A4
Canada
Toll-free: 1-800-665-3223
Telephone: +1-416-597-2229
Fax: +1-416-597-8494
E-mail: info@aboutface.ca
Website: https://www.aboutface.ca/
FACES: The National Craniofacial Association
PO Box 11082
Chattanooga, TN 37401
Toll-free: 800-332-2373
Telephone: 423-266-1632
E-mail: faces@faces-cranio.org
Website: http://www.faces-cranio.org/
Hearing Loss Association of America
7910 Woodmont Avenue
Suite 1200
Bethesda, MD 20814
Telephone: +1-301-657-2248
E-mail: info@hearingloss.org
Website: https://www.hearingloss.org/

Organizations Providing General Support

Restricted Growth Association
P.O. Box 4744
Dorchester
Dorset, Intl DT2 9FA
United Kingdom
Telephone: 01308 898445
Fax: 01308 898445
Website: http://www.restrictedgrowth.co.uk

Do you know of an organization? We want to hear from you.

Learn More 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.

News & Events News & Events

News

Rare Disease Day at NIH 2021
March 1, 2021

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My younger son has Johanson Blizzard syndrome. He has arrested growth, hearing loss, some teeth disappearance and pancreatic insufficiency. He was also diagnosed with pure red cell aplasia. How can we help pancreatic insufficiency, which helps with growth? Is there any help for hearing impairment? See answer

Have a question? Contact a GARD Information Specialist.

References References

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