Shwachman-Diamond syndrome

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Other Names: SDS; Pancreatic insufficiency and bone marrow dysfunction; Shwachman-Bodian syndrome; Lipomatosis of pancreas, congenital; Congenital lipomatosis of pancreas

Shwachman-Diamond syndrome is an inherited condition that affects many parts of the body, particularly the bone marrow, pancreas, and bones.

Epidemiology[edit | edit source]

Shwachman-Diamond syndrome is a rare condition that is thought to occur in approximately 1 in 80,000 newborns. Because the signs and symptoms are variable and can be mild in some affected individuals, doctors suspect the condition is underdiagnosed.

Cause[edit | edit source]

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 that is critical in building ribosomes. Ribosomes are cellular structures that process the cell's genetic instructions to create proteins. SBDS gene mutations reduce the amount or impair the function of the SBDS protein. It is unclear how these changes lead to the major signs and symptoms of Shwachman-Diamond syndrome. Researchers suspect that a shortage of functional SBDS impairs ribosome formation, which may reduce the production of other proteins and alter developmental processes.

Other genes involved in Shwachman-Diamond syndrome appear to play roles in the assembly or function of ribosomes. Mutations in each of these genes account for a very small percentage of cases of the condition. In some cases, no mutations in any of the genes associated with the condition are found, and the cause of the disorder is unknown.

Inheritance[edit | edit source]

Most cases of Shwachman-Diamond syndrome, including those caused by mutations in the SBDS gene, are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Typically, the parents of the affected individual each carry one copy of the mutated gene, but they do not show signs and symptoms of the condition. In some cases, one parent does not carry a copy of the mutated gene. Instead a new (de novo) mutation occurs in the gene during the formation of reproductive cells (eggs or sperm) in the parent or during early embryonic development.

Rarely, the condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. These cases usually result from de novo mutations in the gene and occur in people with no history of the disorder in their family.

Signs and symptoms[edit | edit source]

In Shwachman-Diamond syndrome, the bone marrow malfunctions and does not make some or all types of white blood cells. A shortage of neutrophils, the most common type of white blood cell, causes a condition called neutropenia. Most people with Shwachman-Diamond syndrome have at least occasional episodes of neutropenia, which makes them more vulnerable to infections, often involving the lungs (pneumonia), ears (otitis media), or skin. Less commonly, bone marrow abnormalities lead to a shortage of red blood cells (anemia), which causes fatigue and weakness, or a reduction in the amount of platelets (thrombocytopenia), which can result in easy bruising and abnormal bleeding.

People with Shwachman-Diamond syndrome have an increased risk of several serious complications related to their malfunctioning bone marrow. Specifically, they have a higher-than-average chance of developing myelodysplastic syndrome (MDS) and aplastic anemia, which are disorders caused by abnormal blood stem cells, and a cancer of blood-forming tissue known as acute myeloid leukemia (AML).

Shwachman-Diamond syndrome also affects the pancreas, which is an organ that plays an essential role in digestion. One of this organ's main functions is to produce enzymes that help break down and use nutrients from food. In most infants with Shwachman-Diamond syndrome, the pancreas does not produce enough of these enzymes. This condition is known as pancreatic insufficiency. Infants with pancreatic insufficiency have trouble digesting food and absorbing nutrients and vitamins that are needed for growth. As a result, they often have fatty, foul-smelling stools (steatorrhea); are slow to grow and gain weight (failure to thrive); and experience malnutrition. Pancreatic insufficiency often improves with age in people with Shwachman-Diamond syndrome.

Skeletal abnormalities are another common feature of Shwachman-Diamond syndrome. Many affected individuals have problems with bone formation and growth, most often affecting the hips and knees. Low bone density is also frequently associated with this condition. Some affected infants are born with a narrow rib cage and short ribs, which can cause life-threatening problems with breathing. The combination of skeletal abnormalities and slow growth results in short stature in most people with this disorder.

The complications of Shwachman-Diamond syndrome can affect several other parts of the body, including the liver, heart, endocrine system (which produces hormones), eyes, teeth, and skin. Additionally, studies suggest that Shwachman-Diamond syndrome may be associated with delayed speech and the delayed development of motor skills such as sitting, standing, and walking.

Signs and symptoms may include:

  • Inability to digest food due to lack of digestive enzymes
  • Anemia
  • Low white blood cells (neutropenia)
  • Low platelets (thrombocytopenia)
  • Frequent infections
  • Short stature
  • Rib and/or spine abnormalities
  • Intellectual disability

Babies with SDS have poor feeding, slow growth, and frequent infections. These may get better with age. Many people with SDS have developmental and intellectual delay. Because of bone marrow that doesn't work correctly, people with SDS may be at increased risk for certain blood disorders and cancer.

Diagnosis[edit | edit source]

The diagnosis of Shwachman-Diamond syndrome is based on a clinical exam and other diagnostic tests. Blood tests to look at the white blood cells, red blood cells, and platelets may be helpful. Other tests may be done to check for the function of the pancreas, liver, and kidneys. Genetic testing may be used to confirm the diagnosis.

Treatment[edit | edit source]

Treatment for Shwachman-Diamond syndrome (SDS) is based on managing the symptoms. Treatment options include replacement of missing pancreatic enzymes to aid digestion and a special diet that includes fat-soluble vitamins. Additional treatments include blood transfusions and antibiotics. In cases with severe blood disease, a hematopoietic stem cell transplant may be an option.

Neutropenia may be treated with granulocyte-colony stimulating factor (GCSF) to boost peripheral neutrophil counts. However, there is ongoing and unresolved concern that this drug could contribute to the development of leukemia. Signs of progressive marrow failure may warrant bone marrow transplantation (BMT). This has been used successfully to treat hematological aspects of disease. However, SDS patients have an elevated occurrence of BMT-related adverse events, including graft-versus-host disease (GVHD) and toxicity relating to the pre-transplant conditioning regimen. In the long run, study of the gene that is mutated in SDS should improve understanding of the molecular basis of disease. This, in turn, may lead to novel therapeutic strategies, including gene therapy and other gene- or protein-based approaches.

NIH genetic and rare disease info[edit source]

Shwachman-Diamond syndrome is a rare disease.


Shwachman-Diamond syndrome Resources

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