Shwachman-Diamond syndrome

Title

Other Names:

SDS; Pancreatic insufficiency and bone marrow dysfunction; Shwachman-Bodian syndrome; SDS; Pancreatic insufficiency and bone marrow dysfunction; Shwachman-Bodian syndrome; Lipomatosis of pancreas, congenital; Congenital lipomatosis of pancreas See More

Categories:

Blood Diseases; Congenital and Genetic Diseases; Digestive Diseases; Blood Diseases; Congenital and Genetic Diseases; Digestive Diseases; Immune System Diseases; Musculoskeletal Diseases; Rare Cancers See More

Summary Summary

Shwachman-Diamond syndrome is an inherited condition that affects many parts of the body, particularly the bone marrow, pancreas, and skeletal system.^[1]^[2] Most cases of Shwachman-Diamond syndrome are caused by mutations in the SBDS gene.^[1]8307] In cases where no SBDS mutation is found, the cause of this disorder is unknown.^[1] This condition is inherited in an autosomal recessive manner.^[1]^[3] Treatment may include enzyme and vitamin supplementation, blood and/or platelet transfusion, administration of granulocyte-colony stimulating factor (G-CSF), and/or hematopoietic stem cell transplantation.^[3]

Last updated: 6/23/2015

Symptoms Symptoms

Shwachman-Diamond syndrome is typically characterized by signs of insufficient absorption (malabsorption) of fats and other nutrients due to abnormal development of the pancreas (pancreatic insufficiency) and impaired functioning of the bone marrow, resulting in low levels of circulating blood cells (hematologic abnormalities). Additional characteristic findings may include short stature; abnormal bone development affecting the rib cage and/or bones in the arms and/or legs (metaphyseal dysostosis); recurrent infections; and/or liver dysfunction.^[1]^[2]^[3]

As a result of the bone marrow dysfunction, individuals with Shwachman-Diamond syndrome have a higher-than-average chance of developing myelodysplastic syndrome (MDS) and aplastic anemia, which are disorders that affect blood cell production, and a cancer of blood-forming tissue known as acute myeloid leukemia (AML).^[1]

Last updated: 6/9/2017

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Exocrine pancreatic insufficiency	Very frequent (present in 80%-99% of cases)
Generalized hypotonia	Very frequent (present in 80%-99% of cases)
Neutropenia	Very frequent (present in 80%-99% of cases)
Abnormality of the metaphysis	Frequent (present in 30%-79% of cases)
Anemia	Frequent (present in 30%-79% of cases)
Delayed skeletal maturation	Frequent (present in 30%-79% of cases)
Eczema	Frequent (present in 30%-79% of cases)
Failure to thrive	Frequent (present in 30%-79% of cases)
Ichthyosis	Frequent (present in 30%-79% of cases)
Intellectual disability	Frequent (present in 30%-79% of cases)
Malabsorption	Frequent (present in 30%-79% of cases)
Osteopenia	Frequent (present in 30%-79% of cases)
Recurrent infections	Frequent (present in 30%-79% of cases)
Thrombocytopenia	Frequent (present in 30%-79% of cases)
Acute myeloid leukemia	Occasional (present in 5%-29% of cases)
Aplastic anemia	Occasional (present in 5%-29% of cases)
Bone marrow hypocellularity	Occasional (present in 5%-29% of cases)
Carious teeth	Occasional (present in 5%-29% of cases)
Gait disturbance	Occasional (present in 5%-29% of cases)
Hepatomegaly	Occasional (present in 5%-29% of cases)
Microdontia	Occasional (present in 5%-29% of cases)
Myelodysplasia	Occasional (present in 5%-29% of cases)
Pectus carinatum	Occasional (present in 5%-29% of cases)
Recurrent aphthous stomatitis	Occasional (present in 5%-29% of cases)
Scoliosis	Occasional (present in 5%-29% of cases)
Short thorax	Occasional (present in 5%-29% of cases)
Type I diabetes mellitus	Occasional (present in 5%-29% of cases)
Anterior rib cupping	Very rare (present in 1%-4% of cases)
Proximal femoral metaphyseal irregularity	Very rare (present in 1%-4% of cases)
Autosomal recessive inheritance	-
Coxa vara	-
Elevated hepatic transaminases	-
Enlargement of the costochondral junction	-
Intellectual disability, mild	-
Irregular ossification at anterior rib ends	-
Metaphyseal chondrodysplasia	-
Metaphyseal sclerosis	-
Metaphyseal widening	-
Myocardial necrosis	-
Narrow chest	-
Narrow sacroiliac notch	-
Neonatal respiratory distress	-
Nephrocalcinosis	-
Ovoid vertebral bodies	-
Pancytopenia	-
Persistence of hemoglobin F	-
Proximal femoral epiphysiolysis	-
Small for gestational age	-
Specific learning disability	-
Steatorrhea	-

Last updated: 9/1/2017

Cause Cause

Mutations in the SBDS gene have been identified in about 90 percent of people with the characteristic features of Shwachman-Diamond syndrome. This gene provides instructions for making a protein (the SBDS protein) which is believed to play a role in processing RNA (a molecule that is a chemical cousin of DNA). This protein may also be involved in building ribosomes, which are cellular structures that process the cell's genetic instructions to create proteins.^[1]^[3] Researchers are still trying to understand how SBDS mutations lead to the major signs and symptoms of Shwachman-Diamond syndrome.^[1]

In cases where no SBDS mutation is found, the cause of this disorder is unknown.^[1]

Last updated: 6/9/2017

Inheritance Inheritance

Each brother or sister of a carrier of Shwachman-Diamond syndrome has a 50% chance of being a carrier (having the gene mutation) and a 50% chance of not being a carrier.

If a relative is known to carry an SBDS mutation, other family members can consider genetic testing to determine whether they are carriers. Meeting with a genetics professional can help determine what, if any, genetic testing is appropriate.

Last updated: 2/11/2015

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene (called carriers), but they typically do not show signs and symptoms of the condition.^[1]^[3]

The mode or type of inheritance of Shwachman-Diamond syndrome in individuals without an identified SBDS mutation is unknown.^[3]

Last updated: 6/9/2017

Diagnosis Diagnosis

The diagnosis of Shwachman-Diamond syndrome relies on clinical findings, including pancreatic dysfunction and characteristic hematologic abnormalities. Variation in severity and clinical findings may complicate the ability to establish a definitive diagnosis. Genetic testing may be used to confirm the diagnosis.^[3]

In addition to a complete history and physical examination, other diagnostic tests may be used to aid in the diagnosis of this condition. Blood work may be performed to evaluate the white blood cells, red blood cells, and platelets under a microscope. Blood testing may also evaluate the function of the kidney, liver, and pancreas. Studies such as pancreatic stimulation testing and stool collection may also be performed. A skeletal survey may be done to evaluate the bones of the body. In addition, samples of bone marrow may be taken to examine blood cell lines (red cells, white cells, and platelets), genetic make up of the bone marrow, and the physical architecture of the bone marrow.^[4]

More details regarding the diagnosis of Shwachman-Diamond syndrome can be obtained from the GeneReviews report on this condition.

Last updated: 6/9/2017

Genetic testing is available for SBDS, the gene known to cause most cases of Shwachman-Diamond syndrome (SDS).^[3] Carrier testing for at-risk relatives and prenatal testing are possible if both disease-causing changes (mutations) in the family are known.

In less than 10% of people with SDS, no mutation in the SBDS gene is identified.^[3] The exact underlying cause of the condition in these cases is unknown. Genetic testing is not an option for these families.

Last updated: 6/9/2017

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

There is no cure for Shwachman-Diamond syndrome (SDS). The treatment is directed to the symptoms or signals that the patient has. It is important to have several specialists taking care of the patients, like hematologists, gastroenterologists, geneticists, orthopedics, endocrinologists, immunologists or others, as needed. The treatment may include:^[3]^[5]

• Oral pancreatic enzyme replacement with meals in those who are pancreatic insufficient.
• Supplementation with fat-soluble vitamins (A, D, E, and K) and a low fat diet.
• Blood and/or platelet transfusions may be done if the patient is anemic or have low white cell counts in the blood. • Antibiotics and granulocyte-colony stimulation factor (G-CSF) if there are infections and the white cell blood count are low (500/mm3 or less).
• Hematopoietic stem cell transplantation (HSCT), which are cells that are isolated from the blood or bone marrow and can renew themselves, in cases of severe pancytopenia (low of all blood cells), myelodysplastic syndrome, or acute myelogenous leukemia (AML).
• Use of medicines to treat cancer (chemotherapy) before doing the HSCT when the patient have acute myelogenous leukemia.
• Growth hormone has been used to treat children with Shwachman-Diamond syndrome who have growth hormone deficiency.

Bone marrow abnormalities are not treated unless there is severe aplasia or myelodysplastic changes, or AML. Some children who have bone abnormalities may need surgery if they have respiratory problems (rib problems resulting in asphyxiating thoracic dystrophy), asymmetric growth or joint problems. It is recommended to have consultation with an endocrinologist if the child is having poor growth and delayed puberty, as well as frequent visits to the dentist to reduce the chances of having mouth wounds (ulcers) and gingivitis.^[3]

Last updated: 6/23/2015

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Shwachman-Diamond syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

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

Shwachman-Diamond America
931-B South Main Street #332
Kernersville, NC 27284
Telephone: 336-423-8158
E-mail: shwachmandiamondamerica@embarqmail.com
Website: http://www.shwachmandiamondamerica.org/index.html
Shwachman-Diamond Syndrome Foundation
P.O. Box 40
Avon, NY 14414
Toll-free: 888-825-SDSF (7373)
E-mail: info@shwachman-diamond.org
Website: http://www.shwachman-diamond.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics 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 GeneTests, 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 Genetics Home Reference.

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

Genetics Home Reference (GHR) contains information on Shwachman-Diamond syndrome. This website is maintained by the National Library of Medicine.
The National Cancer Institute provides the most current information on cancer for patients, health professionals, and the general public.
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

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
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 Shwachman-Diamond syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017
Young Investigator Initiative Career Development and Grant Mentoring Program
June 21, 2016

Other Conferences

Shwachman Diamond Syndrome International Congress, June 28, 2011 - June 30, 2011
Location: New York Academy of Science , New York, NY
Description: This biannual Congress - the only multidisciplinary forum devoted specifically to SDS - will explore the most important recent advances in our understanding of the clinical features, current management, and treatment of SDS, and the molecular function of SBDS in hematopoiesis, leukemogenesis, and organogenesis, via a series of plenary lectures, poster sessions, interactive panel discussions, and workshops. Shwachman-Diamond Syndrome patients and their caregivers are eligible to register at a discounted registration rate. For more information, please contact Ms. Deanna Vollmer at 212.298.8611.

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

I have a niece who has this syndrome, and both parents are carriers of a mutation. If my brother is a carrier of the gene mutation, can I be a carrier too? See answer
If one child has Shwachman-Diamond syndrome, will the second child have it as well if the parents are the same? See answer
How is the diagnosis of Shwachman-Diamond syndrome confirmed? See answer
What is Shwachman-Diamond syndrome and what causes it? See answer