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PubMed This is a summary of 41 peer-reviewed journal articles Updated
Gastroenterology

Johanson-Blizzard Syndrome: A Patient Guide

At a Glance

Johanson-Blizzard syndrome is a rare disorder caused by changes in both copies of UBR1. It often affects pancreatic digestion and may affect hearing, facial development, the thyroid, bones, and developmental milestones, so children benefit from coordinated long-term specialist care.

Johanson-Blizzard Syndrome (JBS) is an exceptionally rare genetic disorder that affects multiple systems within the body from the earliest stages of development. At its biological core, JBS is caused by mutations in both copies of the UBR1 gene, which acts as an E3 ubiquitin ligase in the N-end rule pathway—a critical “quality control” process for proteins within cells [1][2]. When this process is disrupted, it leads to the characteristic physical and internal features of the syndrome, most notably affecting the development of the pancreas and facial structures [3][4].

The condition is defined by a combination of hallmark features that require lifelong attention and specialized care. Most children with JBS have exocrine pancreatic insufficiency (EPI), meaning the pancreas cannot produce the enzymes necessary to digest fats and proteins properly [5][6]. This is accompanied by distinct physical markers, such as hypoplastic nasal alae (underdeveloped or small nostrils), and a high likelihood of sensorineural hearing loss [4][7].

Beyond these core features, JBS is known for its significant variability; it can affect the thyroid, the skeletal system, and the way a child reaches developmental milestones in ways that differ even between siblings [8][9]. Because the syndrome touches so many different aspects of health, the standard of care involves a multidisciplinary team of specialists—including gastroenterologists, endocrinologists, and audiologists—who work together to monitor growth and development [8][10].

While a diagnosis of such a rare condition is undoubtedly overwhelming, the focus of modern management is on proactive and practical interventions. By replacing missing enzymes to support nutrition, utilizing hearing technology or sign language to enhance communication, and providing early therapeutic support for development, families and medical teams can improve the child’s quality of life. It is important to know that long-term outcome data on JBS are limited, and outcomes are highly individual. The path forward is built on a foundation of coordinated care and a deep understanding of your child’s unique needs [6][8].

In this guide

6 chapters

01

Orientation to Johanson-Blizzard Syndrome

Learn what Johanson-Blizzard syndrome means for your infant, including UBR1 inheritance, pancreatic enzymes, hearing and thyroid screening, and specialist care.

02

The Biology and Diagnosis of JBS

Learn how UBR1 mutations cause Johanson-Blizzard syndrome, how autosomal recessive inheritance works, and which tests help confirm diagnosis in children.

03

Physical Features and Multisystem Symptoms

Learn about Johanson-Blizzard syndrome symptoms, including nasal and scalp features, thyroid problems, growth, dental changes, and internal organ differences.

04

Managing Digestion and Nutrition

Learn how Johanson-Blizzard syndrome can cause pancreatic insufficiency in infants, including enzyme therapy, vitamin monitoring, growth checks, and urgent warning signs

05

Hearing Loss and Development

Learn how Johanson-Blizzard syndrome affects hearing, language, and development, including hearing tests, hearing aids, cochlear implants, AAC, and early help.

06

Care Coordination and Long-Term Monitoring

Learn how to coordinate care for a child with Johanson-Blizzard syndrome, including specialist roles, long-term monitoring, visit preparation, and key questions.

Common questions in this guide

What is Johanson-Blizzard syndrome?
Johanson-Blizzard syndrome is a very rare genetic disorder that affects multiple body systems from early development. It most often affects pancreatic digestion and may also affect facial development, hearing, the thyroid, bones, growth, and developmental milestones.
What causes Johanson-Blizzard syndrome?
JBS is caused by changes, or mutations, in both copies of the UBR1 gene. UBR1 helps cells manage proteins, and disruption of this process contributes to the syndrome’s features.
How is pancreatic insufficiency managed in JBS?
Exocrine pancreatic insufficiency means the pancreas does not make enough digestive enzymes for fats and proteins. Replacing the missing enzymes helps support digestion and nutrition, with ongoing monitoring by the child’s care team.
What specialists should care for a child with JBS?
Care is usually coordinated by a multidisciplinary team, which may include a gastroenterologist, endocrinologist, and audiologist. The team can work together to monitor pancreatic function, hearing, growth, thyroid and skeletal health, and development.
Does Johanson-Blizzard syndrome affect every child in the same way?
No. Features can vary substantially, even between siblings, and may involve the thyroid, skeleton, hearing, and developmental milestones in different ways. Long-term outcomes are limited in the available data and are highly individual.
How can hearing and development be supported in JBS?
Hearing technology or sign language can support communication when hearing loss is present. Early therapeutic support can help address developmental needs, while the care team monitors progress over time.
Who coordinates care for a child with Johanson-Blizzard syndrome?
Because JBS affects several body systems, families can ask which clinician will serve as the lead care coordinator. That coordinator can help connect the family with gastroenterology, endocrinology, audiology, and other needed services.

Questions For You

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Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Given the rarity of JBS, how will you help us connect with other specialists who have experience with this syndrome?
  2. 2.What are the most immediate priorities for my child's care in the coming weeks?
  3. 3.How does my child's specific UBR1 mutation profile influence our monitoring plan?
  4. 4.Who will serve as the lead care coordinator for my child?

References

References (10)
  1. 1

    Expanding the mutational spectrum in Johanson-Blizzard syndrome: identification of whole exon deletions and duplications in the UBR1 gene by multiplex ligation-dependent probe amplification analysis.

    Sukalo M, Schäflein E, Schanze I, et al.

    Molecular genetics & genomic medicine 2017; (5(6)):774-780 doi:10.1002/mgg3.319.

    PMID: 29178640
  2. 2

    Bound Waters Mediate Binding of Diverse Substrates to a Ubiquitin Ligase.

    Muñoz-Escobar J, Matta-Camacho E, Cho C, et al.

    Structure (London, England : 1993) 2017; (25(5)):719-729.e3 doi:10.1016/j.str.2017.03.004.

    PMID: 28392261
  3. 3

    Clinical Characteristics and Genetic Causes of Infantile Exocrine Pancreatic Insufficiency in Chinese Patients: Study From a Tertiary Care Center.

    Ye Z, Zhou Y, Huang Y, et al.

    Pancreas 2018; (47(10)):1344-1349 doi:10.1097/MPA.0000000000001185.

    PMID: 30308536
  4. 4

    Oblique facial clefts in Johanson-Blizzard syndrome.

    Corona-Rivera JR, Zapata-Aldana E, Bobadilla-Morales L, et al.

    American journal of medical genetics. Part A 2016; (170(6)):1495-501 doi:10.1002/ajmg.a.37630.

    PMID: 26989884
  5. 5

    Variable Expressivity in Johanson-Blizzard Syndrome: A Case With Severe Manifestations and a Review of the Literature.

    Ktyman H, Chaker D, Ahmad H, et al.

    JGH open : an open access journal of gastroenterology and hepatology 2025; (9(8)):e70236 doi:10.1002/jgh3.70236.

    PMID: 40735003
  6. 6

    Johanson-Blizzard Syndrome: A Case Report From Bahrain With a Literature Review.

    Isa HM, Khudhair ZA, Abdulla KM, et al.

    Cureus 2024; (16(3)):e55969 doi:10.7759/cureus.55969.

    PMID: 38606259
  7. 7

    Audiological Profiling and Rehabilitation Outcomes in a Child With Johanson-Blizzard Syndrome.

    Raza AF, Paudel DR, Nisha KV

    Journal of audiology & otology 2022; (26(3)):160-165 doi:10.7874/jao.2021.00444.

    PMID: 34775698
  8. 8

    Three Yemeni Siblings With Johanson-Blizzard Syndrome: A Case Report and Literature Review.

    Abukammas SJ, Abdelgalil A, Shazly MA, et al.

    Cureus 2026; (18(2)):e103579 doi:10.7759/cureus.103579.

    PMID: 41846647
  9. 9

    Johanson-Blizzard syndrome caused by novel UBR1 mutation in four Saudi patients.

    Noli K, Aleysae N, Alzahrani I, et al.

    JPGN reports 2024; (5(2)):140-147 doi:10.1002/jpr3.12057.

    PMID: 38756130
  10. 10

    Shwachman Diamond syndrome: narrow genotypic spectrum and variable clinical features.

    Thompson AS, Giri N, Gianferante DM, et al.

    Pediatric research 2022; (92(6)):1671-1680 doi:10.1038/s41390-022-02009-8.

    PMID: 35322185

This page explains Johanson-Blizzard syndrome for informational purposes only and does not constitute medical advice. Your child’s multidisciplinary care team should guide decisions about enzyme replacement, hearing support, development, and monitoring.